Jing-Yu Pan, Chengcao Sun, Shu-Jun Li, Junchao Huang, Dejia Li
MiR-10b was overexpressed in various cancers, including NSCLC. In early study, miR-10b was described as a carcinoma enhancer in NSCLC. Our recent study showed that silencing of miR-10b could promote NSCLC cells apoptosis and decrease proliferation, and regulation of these cell behaviors might target Klotho via miR-10b. In addition, we also explored the correlation between miR-10b and Klotho or other underlying targets. Our investigation indicated that miR-10b could play a critical role as a helpful prognosis marker and underlying target in terms of therapy of NSCLC.
{"title":"Role of miR-10b in non-small cell lung cancer (NSCLC) cells by targeting Klotho","authors":"Jing-Yu Pan, Chengcao Sun, Shu-Jun Li, Junchao Huang, Dejia Li","doi":"10.14800/CCM.936","DOIUrl":"https://doi.org/10.14800/CCM.936","url":null,"abstract":"MiR-10b was overexpressed in various cancers, including NSCLC. In early study, miR-10b was described as a carcinoma enhancer in NSCLC. Our recent study showed that silencing of miR-10b could promote NSCLC cells apoptosis and decrease proliferation, and regulation of these cell behaviors might target Klotho via miR-10b. In addition, we also explored the correlation between miR-10b and Klotho or other underlying targets. Our investigation indicated that miR-10b could play a critical role as a helpful prognosis marker and underlying target in terms of therapy of NSCLC.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85338297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Mourah, Farah Khayati, Ibtissem Djaafri, J. Delyon, C. R. D. Moura, J. Tost, C. Lebbé, S. Ménashi
Kindlin-3 (FERMT-3) is a key integrin activating protein belonging to the Kindlin family which includes three members Kindlin-1, 2 and 3. Kindlins can directly bind to various classes of integrins and participate in their activation, thus playing a key role in the regulation of cell-matrix adhesions. Kindlin-3 has been known to be central in the control of hemostasis and thrombosis as its deficiency disrupts platelet aggregation and causes Leukocyte Adhesion Deficiency disease. Its expression has so far been only described in hematopoietic cells, and more recently in endothelial cells. The current manuscript highlights key findings from our recent research describing a novel role of Kindlin-3 as a tumor suppressor in cancer. We present data showing that Kindlin-3 is expressed more ubiquitously than previously thought, and that through gene inactivation mechanisms, its expression is significantly reduced in several human solid cancer lesions. The increase in the malignant properties of tumor cells when Kindlin-3 expression is silenced and the inverse expression of Kindlin-3 with the tumor promoter EMMPRIN/CD147 corroborate the tumor suppressor role of Kindlin-3. A schematic model based on our research data describing Kindlin-3 mode of action in tumor cells is presented.
{"title":"A novel function of Kindlin-3 in cancer","authors":"S. Mourah, Farah Khayati, Ibtissem Djaafri, J. Delyon, C. R. D. Moura, J. Tost, C. Lebbé, S. Ménashi","doi":"10.14800/CCM.878","DOIUrl":"https://doi.org/10.14800/CCM.878","url":null,"abstract":"Kindlin-3 (FERMT-3) is a key integrin activating protein belonging to the Kindlin family which includes three members Kindlin-1, 2 and 3. Kindlins can directly bind to various classes of integrins and participate in their activation, thus playing a key role in the regulation of cell-matrix adhesions. Kindlin-3 has been known to be central in the control of hemostasis and thrombosis as its deficiency disrupts platelet aggregation and causes Leukocyte Adhesion Deficiency disease. Its expression has so far been only described in hematopoietic cells, and more recently in endothelial cells. The current manuscript highlights key findings from our recent research describing a novel role of Kindlin-3 as a tumor suppressor in cancer. We present data showing that Kindlin-3 is expressed more ubiquitously than previously thought, and that through gene inactivation mechanisms, its expression is significantly reduced in several human solid cancer lesions. The increase in the malignant properties of tumor cells when Kindlin-3 expression is silenced and the inverse expression of Kindlin-3 with the tumor promoter EMMPRIN/CD147 corroborate the tumor suppressor role of Kindlin-3. A schematic model based on our research data describing Kindlin-3 mode of action in tumor cells is presented.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76858106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leukemia inhibitory factor (LIF), a secreted cytokine, plays an important role in a wide array of biological processes including inducing differentiation of leukemia cell, inflammatory response, neuronal development, embryonic implantation, stem cell self-renewal and cancer progression, etc. LIF exerts its biological functions mainly through the activation and regulation of JAK/STAT3, AKT, EKR1/2 and mTOR signal pathways. The expression levels of LIF are regulated by many different factors under different conditions in different tissue/cell types. For example, estrogen and p53 are important regulators for the high LIF production in uterine tissues at the implantation stage. Hypoxia plays a critical role in LIF overexpression in solid tumors. Many cytokines, including IL-6, IL-1β, can also induce the LIF expression and production. In this review, we summarize the current understanding on the transcriptional regulation of LIF under various conditions.
{"title":"The regulation of leukemia inhibitory factor.","authors":"Xuetian Yue, Lihua Wu, Wenwei Hu","doi":"10.14800/CCM.877","DOIUrl":"https://doi.org/10.14800/CCM.877","url":null,"abstract":"Leukemia inhibitory factor (LIF), a secreted cytokine, plays an important role in a wide array of biological processes including inducing differentiation of leukemia cell, inflammatory response, neuronal development, embryonic implantation, stem cell self-renewal and cancer progression, etc. LIF exerts its biological functions mainly through the activation and regulation of JAK/STAT3, AKT, EKR1/2 and mTOR signal pathways. The expression levels of LIF are regulated by many different factors under different conditions in different tissue/cell types. For example, estrogen and p53 are important regulators for the high LIF production in uterine tissues at the implantation stage. Hypoxia plays a critical role in LIF overexpression in solid tumors. Many cytokines, including IL-6, IL-1β, can also induce the LIF expression and production. In this review, we summarize the current understanding on the transcriptional regulation of LIF under various conditions.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"115 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76147367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pathological angiogenesis occurs when the balance between pro-angiogenic and anti-angiogenic factors is tipped enabling an angiogenic switch. VEGF-A is the primary inducer of angiogenesis but is alternatively spliced at the pre-mRNA level to produce pro-angiogenic and anti-angiogenic isoforms. In previous work we showed that the balance of VEGF-A isoforms is regulated by SRSF1, which is regulated by phosphorylation from SRPK1 in renal epithelial cells, colon cancer cells, retinal epithelial cells and melanoma cells. SRPK1 and SRSF1 promote expression of pro-angiogenic VEGF-A 165 a and knockdown or inhibition of SRPK1 switches this balance towards anti-angiogenic VEGF-A 165 b, which inhibits angiogenesis and tumor growth in colon cancer and melanoma cells. In our recent study, Mavrou et al ., 2014, we report that SRPK1 expression is upregulated in both prostatic intraepithelial neoplasia and malignant tissue sections from patients with radical prostatectomy. Knockdown or inhibition of SRPK1 with small molecule inhibitors leads to a splicing switch towards anti-angiogenic VEGF-A in PC-3 cells, a reduction in angiogenesis and inhibition of tumor growth in xenograft models. Specifically inhibiting pro-angiogenic VEGF-A splice isoforms through targeted inhibition of the splicing kinase SRPK1 is a novel approach which could enable development of therapies that are safer and more efficacious than current drugs. This study provides proof-of-concept for modulation of SRPK1 to normalise the endogenous VEGF-A splicing balance, enabling inhibition of angiogenesis and tumor growth in prostate cancer. Here, we discuss our recent findings and ongoing work to develop these findings into a novel therapeutic approach.
{"title":"Targeting the angiogenic 'splice' switch; inhibition of SRPK1 as a novel therapeutic approach in prostate cancer","authors":"J. Batson, S. Oltean, D. Bates","doi":"10.14800/CCM.876","DOIUrl":"https://doi.org/10.14800/CCM.876","url":null,"abstract":"Pathological angiogenesis occurs when the balance between pro-angiogenic and anti-angiogenic factors is tipped enabling an angiogenic switch. VEGF-A is the primary inducer of angiogenesis but is alternatively spliced at the pre-mRNA level to produce pro-angiogenic and anti-angiogenic isoforms. In previous work we showed that the balance of VEGF-A isoforms is regulated by SRSF1, which is regulated by phosphorylation from SRPK1 in renal epithelial cells, colon cancer cells, retinal epithelial cells and melanoma cells. SRPK1 and SRSF1 promote expression of pro-angiogenic VEGF-A 165 a and knockdown or inhibition of SRPK1 switches this balance towards anti-angiogenic VEGF-A 165 b, which inhibits angiogenesis and tumor growth in colon cancer and melanoma cells. In our recent study, Mavrou et al ., 2014, we report that SRPK1 expression is upregulated in both prostatic intraepithelial neoplasia and malignant tissue sections from patients with radical prostatectomy. Knockdown or inhibition of SRPK1 with small molecule inhibitors leads to a splicing switch towards anti-angiogenic VEGF-A in PC-3 cells, a reduction in angiogenesis and inhibition of tumor growth in xenograft models. Specifically inhibiting pro-angiogenic VEGF-A splice isoforms through targeted inhibition of the splicing kinase SRPK1 is a novel approach which could enable development of therapies that are safer and more efficacious than current drugs. This study provides proof-of-concept for modulation of SRPK1 to normalise the endogenous VEGF-A splicing balance, enabling inhibition of angiogenesis and tumor growth in prostate cancer. Here, we discuss our recent findings and ongoing work to develop these findings into a novel therapeutic approach.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"73 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83968719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. Fujiki, K. Imai, K. Nakachi, E. Sueoka, Tatsuro Watanabe, M. Suganuma
Human cancer development involves durable genetic changes caused by carcinogens, pro-inflammatory cytokines and chemokines, and simultaneous inflammation in cancer microenvironment. Green tea containing non-toxic anti-inflammatory green tea catechins is an acknowledged cancer preventive. This paper first introduces two results that 10 Japanese-size-cups (150 ml/cup) of green tea per day delayed cancer onset in primary cancer prevention and daily green tea supplemented with tablets of green tea extract equivalent to 10 cups prevented colorectal adenoma recurrence in tertiary cancer prevention. The results allowed us to find synergistic anticancer effects in both in vitro and in vivo experiments with the combinations of (-)-epigallocatechin gallate (EGCG) or green tea extract and two non-steroidal anti-inflammatory drugs (NSAIDs), such as sulindac and celecoxib. We next collected the results of numerous investigators as follows: the combinations of EGCG and 37 anticancer compounds, which include NSAIDs, phytochemicals, and anticancer drugs, generally induced in vitro synergistic anticancer effects on 54 human cancer cell lines derived from various cancer tissues, and the combinations of EGCG, or green tea extract and 13 anticancer compounds showed reduction of tumor volume in xenograft mouse models implanted using various human cancer cell lines. For example, average reduction of tumor volume with combinations, anticancer compounds alone, EGCG alone, or vehicle for control were 70.3%, 33.7%, 26.5%, or 0%, respectively. Especially, the complete elimination of tumor development on human prostate cancer cell line PC-3ML was found in xenograft mouse models treated with combinations of EGCG and paclitaxel, and EGCG and docetaxel. The amount of EGCG necessary for complete elimination of tumor in mice corresponds to 6 - 9 cups of green tea for humans. Moreover, the combination was reported to inhibit stem cell characteristics. The combination resulting in 70.3% reduction of tumor volume makes it possible to innovate cancer treatment, and the cancer patient could achieve improved quality of life without suffering the side effects of anticancer drugs, which results in “the final goal of cancer therapy is the survival of cancer patients with coexistence of cancer cells” presented by Prof. Tomizo Yoshida, a mentor of Japanese pathologists.
{"title":"Innovative strategy of cancer treatment with the combination of green tea catechins and anticancer compounds","authors":"H. Fujiki, K. Imai, K. Nakachi, E. Sueoka, Tatsuro Watanabe, M. Suganuma","doi":"10.14800/CCM.886","DOIUrl":"https://doi.org/10.14800/CCM.886","url":null,"abstract":"Human cancer development involves durable genetic changes caused by carcinogens, pro-inflammatory cytokines and chemokines, and simultaneous inflammation in cancer microenvironment. Green tea containing non-toxic anti-inflammatory green tea catechins is an acknowledged cancer preventive. This paper first introduces two results that 10 Japanese-size-cups (150 ml/cup) of green tea per day delayed cancer onset in primary cancer prevention and daily green tea supplemented with tablets of green tea extract equivalent to 10 cups prevented colorectal adenoma recurrence in tertiary cancer prevention. The results allowed us to find synergistic anticancer effects in both in vitro and in vivo experiments with the combinations of (-)-epigallocatechin gallate (EGCG) or green tea extract and two non-steroidal anti-inflammatory drugs (NSAIDs), such as sulindac and celecoxib. We next collected the results of numerous investigators as follows: the combinations of EGCG and 37 anticancer compounds, which include NSAIDs, phytochemicals, and anticancer drugs, generally induced in vitro synergistic anticancer effects on 54 human cancer cell lines derived from various cancer tissues, and the combinations of EGCG, or green tea extract and 13 anticancer compounds showed reduction of tumor volume in xenograft mouse models implanted using various human cancer cell lines. For example, average reduction of tumor volume with combinations, anticancer compounds alone, EGCG alone, or vehicle for control were 70.3%, 33.7%, 26.5%, or 0%, respectively. Especially, the complete elimination of tumor development on human prostate cancer cell line PC-3ML was found in xenograft mouse models treated with combinations of EGCG and paclitaxel, and EGCG and docetaxel. The amount of EGCG necessary for complete elimination of tumor in mice corresponds to 6 - 9 cups of green tea for humans. Moreover, the combination was reported to inhibit stem cell characteristics. The combination resulting in 70.3% reduction of tumor volume makes it possible to innovate cancer treatment, and the cancer patient could achieve improved quality of life without suffering the side effects of anticancer drugs, which results in “the final goal of cancer therapy is the survival of cancer patients with coexistence of cancer cells” presented by Prof. Tomizo Yoshida, a mentor of Japanese pathologists.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74639379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The role of DICKKOPF (DKK)-1 in human cancer is controversial. DKK-1 behaves as an inhibitor of the canonical Wnt/b-catenin signaling pathway acting at the plasma membrane, although several studies have proposed effects that are independent of the inhibition of b-catenin transcriptional activity, in some cases mediated by the activation of c-Jun N-terminal kinase (JNK). Recently, a proportion of DKK-1 protein has been found within the nucleus of human intestinal epithelial cells following an apical-to-basal crypt decreasing gradient, and in that of colon carcinoma cells. Moreover, we show here that in the human mammary gland DKK-1 is also present within the nucleus of many differentiated luminal epithelial cells and in that of a small proportion of myoepithelial cells. Nuclear DKK-1 binds to actively transcribed chromatin and regulates the expression of specific genes, some of which are involved in cell proliferation, survival and stemness, and in the defense against xenobiotics. This may explain the finding that while DKK-1 is downregulated more rapidly in the nucleus than in the cytosol during colon carcinoma progression, its expression remains high in a percentage of patients who do not respond to chemotherapy. Available data suggest that the accumulation of DKK-1 in the nucleus of colon carcinoma cells depends on signals from the surrounding tumor microenvironment.
DICKKOPF (DKK)-1在人类癌症中的作用尚存争议。DKK-1作为作用于质膜的典型Wnt/b-catenin信号通路的抑制剂，尽管一些研究已经提出了独立于抑制b-catenin转录活性的作用，在某些情况下通过激活c-Jun n -末端激酶(JNK)介导。近年来，在人肠上皮细胞和结肠癌细胞的细胞核中发现了一定比例的DKK-1蛋白，它们呈自上而下的隐窝递减梯度。此外，我们在这里表明，在人乳腺中，DKK-1也存在于许多分化的腔上皮细胞和一小部分肌上皮细胞的细胞核中。核DKK-1结合活性转录的染色质并调节特定基因的表达，其中一些基因参与细胞增殖，存活和干性，以及对外源物的防御。这可能解释了在结肠癌进展过程中，细胞核中的DKK-1比细胞质中的DKK-1下调得更快，但在对化疗无反应的患者中，DKK-1的表达仍然很高。现有数据表明，DKK-1在结肠癌细胞核中的积累依赖于来自周围肿瘤微环境的信号。
{"title":"The complex life of DICKKOPF-1 in cancer cells","authors":"J. González-Sancho, F. Rojo, A. Muñoz","doi":"10.14800/CCM.870","DOIUrl":"https://doi.org/10.14800/CCM.870","url":null,"abstract":"The role of DICKKOPF (DKK)-1 in human cancer is controversial. DKK-1 behaves as an inhibitor of the canonical Wnt/b-catenin signaling pathway acting at the plasma membrane, although several studies have proposed effects that are independent of the inhibition of b-catenin transcriptional activity, in some cases mediated by the activation of c-Jun N-terminal kinase (JNK). Recently, a proportion of DKK-1 protein has been found within the nucleus of human intestinal epithelial cells following an apical-to-basal crypt decreasing gradient, and in that of colon carcinoma cells. Moreover, we show here that in the human mammary gland DKK-1 is also present within the nucleus of many differentiated luminal epithelial cells and in that of a small proportion of myoepithelial cells. Nuclear DKK-1 binds to actively transcribed chromatin and regulates the expression of specific genes, some of which are involved in cell proliferation, survival and stemness, and in the defense against xenobiotics. This may explain the finding that while DKK-1 is downregulated more rapidly in the nucleus than in the cytosol during colon carcinoma progression, its expression remains high in a percentage of patients who do not respond to chemotherapy. Available data suggest that the accumulation of DKK-1 in the nucleus of colon carcinoma cells depends on signals from the surrounding tumor microenvironment.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88941275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marco Iuliano, G. Mangino, M. Chiantore, G. Fiorucci, R. Accardi, M. Tommasino, G. Romeo
The inception of tumor microenvironment (TME), a complex and dynamic system constituted by different types of cells engaged by tumor and extracellular matrix surrounding cancer cells, is a way for them to elude the immune surveillance. Dendritic cells (DCs), as a sentinel, are able to recognize alteration in the microenvironment and predispose the immune system response. The relationship between cancer and virus infection is well documented. High-risk Human Papillomavirus (HR-HPV) has a well-characterized transforming property and has been associated with squamous cell carcinoma of the ano-genital and oral tracts. Transforming ability of HR-HPVs is based on the function of E6 and E7 viral oncoproteins, which interact and inactivate p53 and pRb oncosuppressors, respectively. Recently, it was demonstrated that HPV oncoproteins are also able to affect a number of microRNAs (miRNAs) regulating the expression of genes involved in proliferative control. For these reasons DC-based vaccines targeting oncogenic E6 and E7 are ideal candidates to elicit strong immune responses. Here we summarize significant data about the analysis of TME in HPV-induced tumorigenesis. We also report original results produced by cytotoxic T lymphocyte (CTL) in vitro priming against E6 and E7 HPV16 antigens, performed using human monocyte-derived dendritic cells. Dendritic cells, maturated by the exposition to necrotic or apoptotic keratinocytes expressing both oncoproteins of HPV16, show different expression levels of specific maturation markers. Evidence indicating the ability of necrotic keratinocytes to alter the microRNA profile in DCs, macrophages (MΦ) and Langerhans cells (LCs) compared to prototypical stimuli as bacterial lipopolysaccharide was also provided. We can speculate that, based on transformed cells death pathway (i.e. apoptosis versus necrosis), virus-induced immune alterations might show different results in creating an immunotolerogenic microenvironment during the carcinogenesis process.
{"title":"The role of microenvironment in tumorigenesis: Focus on dendritic cells in human papillomavirus E6, E7-transformed keratinocytes","authors":"Marco Iuliano, G. Mangino, M. Chiantore, G. Fiorucci, R. Accardi, M. Tommasino, G. Romeo","doi":"10.14800/CCM.874","DOIUrl":"https://doi.org/10.14800/CCM.874","url":null,"abstract":"The inception of tumor microenvironment (TME), a complex and dynamic system constituted by different types of cells engaged by tumor and extracellular matrix surrounding cancer cells, is a way for them to elude the immune surveillance. Dendritic cells (DCs), as a sentinel, are able to recognize alteration in the microenvironment and predispose the immune system response. The relationship between cancer and virus infection is well documented. High-risk Human Papillomavirus (HR-HPV) has a well-characterized transforming property and has been associated with squamous cell carcinoma of the ano-genital and oral tracts. Transforming ability of HR-HPVs is based on the function of E6 and E7 viral oncoproteins, which interact and inactivate p53 and pRb oncosuppressors, respectively. Recently, it was demonstrated that HPV oncoproteins are also able to affect a number of microRNAs (miRNAs) regulating the expression of genes involved in proliferative control. For these reasons DC-based vaccines targeting oncogenic E6 and E7 are ideal candidates to elicit strong immune responses. Here we summarize significant data about the analysis of TME in HPV-induced tumorigenesis. We also report original results produced by cytotoxic T lymphocyte (CTL) in vitro priming against E6 and E7 HPV16 antigens, performed using human monocyte-derived dendritic cells. Dendritic cells, maturated by the exposition to necrotic or apoptotic keratinocytes expressing both oncoproteins of HPV16, show different expression levels of specific maturation markers. Evidence indicating the ability of necrotic keratinocytes to alter the microRNA profile in DCs, macrophages (MΦ) and Langerhans cells (LCs) compared to prototypical stimuli as bacterial lipopolysaccharide was also provided. We can speculate that, based on transformed cells death pathway (i.e. apoptosis versus necrosis), virus-induced immune alterations might show different results in creating an immunotolerogenic microenvironment during the carcinogenesis process.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84892072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rac1 has been described as a major player in glioma invasion and progression. The development of novel anti Rac1 inhibitors, such as 1A-116, provides a targeted rational approach to counteract glioma progression. This therapeutic strategy could affect the glioma cell behavior as well as its interplay with the microenvironment. Further studies are needed to validate the effectiveness of this novel molecules and their use in glioma progression.
{"title":"Dynamic interaction between glioma cells and their microenvironment: targeting Rac1 as a therapeutic approach","authors":"Georgina A. Cardama, P. Menna","doi":"10.14800/CCM.866","DOIUrl":"https://doi.org/10.14800/CCM.866","url":null,"abstract":"Rac1 has been described as a major player in glioma invasion and progression. The development of novel anti Rac1 inhibitors, such as 1A-116, provides a targeted rational approach to counteract glioma progression. This therapeutic strategy could affect the glioma cell behavior as well as its interplay with the microenvironment. Further studies are needed to validate the effectiveness of this novel molecules and their use in glioma progression.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"15 12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86910794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Breast cancer stem cells (CSC) are small subset of tumor cells within the tumor, possessing distinct immunological phenotype; they initiate the tumor and sustain tumor growth. Epithelial to mesenchymal transition (EMT) is the loss of epithelial differentiation and gained the mesenchymal properties among some of tumor cells. Acquisition of mesenchymal phenotype allows these cells to infiltrate surrounding tissue, which ultimately enhance tumor propagation and progression. EMT occurrence is always co-existent with CSC subsistence. EMT induced by various factors is rich source of cancer stem like cells suggesting a possible biological similarity between CSC and EMT phenotypic cells. The inhibition of EMT occurrence and CSC elimination may have significant effect on cancer prognosis, which could suggest that these cells will be a target for cancer therapeutics. Prospective identification of new molecules and markers for these tumorigenic cells will
乳腺癌干细胞(CSC)是肿瘤内肿瘤细胞的一个小子集，具有独特的免疫表型;它们引发肿瘤并维持肿瘤生长。上皮向间充质转化(Epithelial to mesenchymal transition, EMT)是部分肿瘤细胞失去上皮分化而获得间充质特性的过程。获得间充质表型允许这些细胞浸润周围组织，最终促进肿瘤的增殖和进展。EMT的发生与CSC的生存总是共存的。多种因素诱导的EMT是肿瘤干细胞样细胞的丰富来源，提示CSC与EMT表型细胞之间可能存在生物学相似性。抑制EMT的发生和CSC的消除可能对癌症预后有显著影响，这可能表明这些细胞将成为癌症治疗的靶点。对这些致瘤细胞的新分子和标记物的前瞻性鉴定将会有很大帮助
{"title":"Breast cancer stem cells and epithelial to mesenchymal transition, their putative role in tumor initiation, propagation, and metastasis","authors":"J. Makki","doi":"10.14800/CCM.842","DOIUrl":"https://doi.org/10.14800/CCM.842","url":null,"abstract":"Breast cancer stem cells (CSC) are small subset of tumor cells within the tumor, possessing distinct immunological phenotype; they initiate the tumor and sustain tumor growth. Epithelial to mesenchymal transition (EMT) is the loss of epithelial differentiation and gained the mesenchymal properties among some of tumor cells. Acquisition of mesenchymal phenotype allows these cells to infiltrate surrounding tissue, which ultimately enhance tumor propagation and progression. EMT occurrence is always co-existent with CSC subsistence. EMT induced by various factors is rich source of cancer stem like cells suggesting a possible biological similarity between CSC and EMT phenotypic cells. The inhibition of EMT occurrence and CSC elimination may have significant effect on cancer prognosis, which could suggest that these cells will be a target for cancer therapeutics. Prospective identification of new molecules and markers for these tumorigenic cells will","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"195 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74325793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Chao, Chunlei Zhang, Yanlei Liu, Meng Yang, Jingpu Zhang, Xiao Zhi, Fei Pan, D. Cui
Herein, we report for the first time of the novel vaccine cell composed with allogenic mature dendritic cells (DCs) and inactive gastric cancer (GC) cells prepared by PEG mediated fusion. Combined with effecter of cytokine induced killing cells (CIKs), the immunotherapeutic and prophylactic potential of the fused vaccine cells (VCs) were evaluated in tumor-bearing, post-surgery and tumor free mice models. The migration and homing process of near infrared region quantum dots (NIR-QDs) labeled VCs were investigated by real-time animal imaging system. Results showed that the VCs and VC+CIKs could trigger the tumor-specific CTLs against GC cell, target the tumor tissue initiatively and enhance the prophylactic effects, suppress the tumor growth remarkably in vivo . The potential mechanism is also investigated. In conclusion, the novel vaccine cells can be used for targeted imaging and enhanced immunotherapeutic efficacy of GC, and hopeful to solve the double problems of antigen delivery and host immunity enhancement at the same time.
{"title":"The novel vaccine contained full tumor antigen hopeful to solve the problems of antigen delivery and host immunity enhancement","authors":"L. Chao, Chunlei Zhang, Yanlei Liu, Meng Yang, Jingpu Zhang, Xiao Zhi, Fei Pan, D. Cui","doi":"10.14800/CCM.865","DOIUrl":"https://doi.org/10.14800/CCM.865","url":null,"abstract":"Herein, we report for the first time of the novel vaccine cell composed with allogenic mature dendritic cells (DCs) and inactive gastric cancer (GC) cells prepared by PEG mediated fusion. Combined with effecter of cytokine induced killing cells (CIKs), the immunotherapeutic and prophylactic potential of the fused vaccine cells (VCs) were evaluated in tumor-bearing, post-surgery and tumor free mice models. The migration and homing process of near infrared region quantum dots (NIR-QDs) labeled VCs were investigated by real-time animal imaging system. Results showed that the VCs and VC+CIKs could trigger the tumor-specific CTLs against GC cell, target the tumor tissue initiatively and enhance the prophylactic effects, suppress the tumor growth remarkably in vivo . The potential mechanism is also investigated. In conclusion, the novel vaccine cells can be used for targeted imaging and enhanced immunotherapeutic efficacy of GC, and hopeful to solve the double problems of antigen delivery and host immunity enhancement at the same time.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"279 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77478704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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