Advances in cancer biology - metastasis最新文献_第2页

Effect of gaillardin on the metastatic capacity of breast cancer cells and its underlying mechanism 大蒜素对乳腺癌细胞转移能力的影响及其潜在机制

IF 3 Q3 ONCOLOGY

Advances in cancer biology - metastasis

Pub Date : 2025-12-01 DOI: 10.1016/j.adcanc.2025.100164

Sadegh Rajabi , Akram Shahhosseini , Mahboubeh Irani , Marc Maresca , Maryam Hamzeloo-Moghadam

The metastasis process plays an important role in the outcome of all cancers, including breast cancer, a leading cause of cancer mortality in women. This study assessed the effects of gaillardin on the metastatic activity of two different breast cancer cell lines. The MTT assay was used to obtain the IC₅₀ concentrations. Migration or metastatic capability of MCF7 and MDA-MB231 cell lines was assayed using the wound scratch assay. The real-time PCR was utilized to quantify the gene expression of epithelial-mesenchymal transition (EMT) markers CDH1, CDH2, VIM, and FN1, along with angiogenesis-related markers VEGFA and THBS1. Western blotting was conducted to estimate the protein expression of E-cadherin, N-cadherin, vimentin, fibronectin 1, VEGFA, and thrombospondin 1. Treatment of the MCF7 cell line with different concentrations of gaillardin revealed no significant effect on the metastatic capacity of these cancer cells compared with the controls. However, the migratory activity and aggressiveness of MDA-MB231 cells were significantly hindered compared to the control cells. The results of gene expression data revealed the upregulating effect of gaillardin on the expression of CDH1 and THBS1 genes. Conversely, this phytochemical significantly downregulated CDH2, VIM, FN1, and VEGFA transcripts. Western blotting results showed a similar effect of gaillardin on the expression levels of the above-mentioned markers. The present data highlight the anti-metastatic activity of gaillardin in breast cancer in a receptor-independent manner. These results also indicate gaillardin as a potential anti-metastatic natural compound against triple-negative breast cancer cells, via two mechanisms that act by suppressing EMT and angiogenesis.

转移过程在包括乳腺癌在内的所有癌症的预后中起着重要作用，乳腺癌是女性癌症死亡的主要原因。本研究评估了丁香苷对两种不同乳腺癌细胞系转移活性的影响。采用MTT法测定IC50浓度。采用伤口划痕法检测MCF7和MDA-MB231细胞系的迁移或转移能力。real-time PCR用于定量上皮-间质转化（EMT）标志物CDH1、CDH2、VIM和FN1以及血管生成相关标志物VEGFA和THBS1的基因表达。Western blotting检测E-cadherin、N-cadherin、vimentin、纤维连接蛋白1、VEGFA和血栓反应蛋白1的表达。与对照组相比，用不同浓度的盖拉定治疗MCF7细胞系对这些癌细胞的转移能力没有显著影响。然而，MDA-MB231细胞的迁移活性和侵袭性明显受到抑制。基因表达数据结果显示，盖拉丹对CDH1和THBS1基因的表达有上调作用。相反，这种植物化学物质显著下调CDH2、VIM、FN1和VEGFA转录本。Western blotting结果显示，盖拉定对上述标记物的表达水平有类似的影响。目前的数据强调了盖拉丁在乳腺癌中的抗转移活性是一种不依赖于受体的方式。这些结果还表明，盖拉定是一种潜在的抗转移性天然化合物，可以通过抑制EMT和血管生成两种机制来对抗三阴性乳腺癌细胞。

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引用次数: 0

Corrigendum to “HDAC3-mediated deacetylation of p21 stabilizes protein levels and promotes 5-FU resistance in colorectal cancer cells” [ADCANC (2025) 100136] “hdac3介导的p21去乙酰化稳定结直肠癌细胞的蛋白水平并促进5-FU耐药性”的勘误表[ADCANC (2025) 100136]

IF 3 Q3 ONCOLOGY

Advances in cancer biology - metastasis

Pub Date : 2025-12-01 DOI: 10.1016/j.adcanc.2025.100146

Wei Jin , Jue-jue Wang , Yan-fei Feng , Bing Chen , Zhao-hua Hu

引用次数: 0

Roles of the WNT/β-catenin signaling pathway in the metastasis and recurrence of NSCLC WNT/β-catenin信号通路在NSCLC转移和复发中的作用

IF 3 Q3 ONCOLOGY

Advances in cancer biology - metastasis

Pub Date : 2025-12-01 DOI: 10.1016/j.adcanc.2025.100162

Yi Liu , JiaYing Ma , Jitian Zhang , Qi Sun

Lung cancer is the leading cause of cancer-related death globally and the most common cause of brain metastasis. Non-small cell lung cancer (NSCLC) accounts for approximately 80 % of all lung cancers. High metastasis and recurrence rates are important factors contributing to the poor prognosis of patients with NSCLC. The canonical WNT signaling pathway, as a highly conserved signal transduction pathway, not only directly affects the metastasis and recurrence of NSCLC, but also participates in it by regulating the stemness and epithelial-mesenchymal transition (EMT) process of lung cancer cells, or by interacting with other signaling pathways. In this review, we summarize the direct or indirect functions and mechanisms of roles of the WNT/β-catenin signaling pathway (including WNT ligands, β-catenin, glycogen synthase kinase 3Β, adenomatous polyposis coli, axis inhibition protein, dishevelled, frizzled serpentine receptor, Dickkopf-related protein, lymphoid enhancer-binding factor/T cell-specific factor, and S-phase kinase associated protein 1–cullin–F-box E3 ligase) in NSCLC metastasis and recurrence. Additionally, we explore the potential of inhibitors of this pathway in preventing NSCLC metastasis and recurrence.

肺癌是全球癌症相关死亡的主要原因，也是脑转移的最常见原因。非小细胞肺癌（NSCLC）约占所有肺癌的80%。高转移率和复发率是导致非小细胞肺癌患者预后不良的重要因素。典型的WNT信号通路作为一种高度保守的信号转导通路，不仅直接影响NSCLC的转移和复发，而且通过调节肺癌细胞的干性和上皮-间质转化（EMT）过程，或与其他信号通路相互作用参与NSCLC的转移和复发。本文综述了WNT/β-catenin信号通路（包括WNT配体、β-catenin、糖原合酶激酶3Β、腺瘤性大肠息肉病、轴抑制蛋白、disheveld1、卷曲蛇形受体、dickkopf相关蛋白、淋巴细胞增强因子结合因子/T细胞特异性因子、s期激酶相关蛋白1-cullin-F-box E3连接酶）在NSCLC转移和复发中的直接或间接功能及其作用机制。此外，我们还探讨了该通路抑制剂在预防非小细胞肺癌转移和复发中的潜力。

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引用次数: 0

Corrigendum to “Niosomes containing enciprazine hydrochloride have been shown to efficiently inhibit the proliferation and induce apoptosis in colorectal cancer cells” [Advan. Cancer Biol. Metastasis 12 (2024) 100128] “含有盐酸恩西哌嗪的Niosomes已被证明能有效抑制结直肠癌细胞的增殖并诱导细胞凋亡”[Advan。癌症医学杂志。转移12 (2024)100128]

IF 3 Q3 ONCOLOGY

Advances in cancer biology - metastasis

Pub Date : 2025-12-01 DOI: 10.1016/j.adcanc.2025.100156

Hosain Nasirian , Saeedeh TarvijEslami , Hedieh Ghourchian , Marjaneh Ebrahimi , Tohid Piri-Gharaghie , Ghazal Ghajari

引用次数: 0

Repurposing statins in combination therapy for effective ablation of metastatic breast cancer 他汀类药物联合治疗对转移性乳腺癌的有效消融

IF 3 Q3 ONCOLOGY

Advances in cancer biology - metastasis

Pub Date : 2025-11-27 DOI: 10.1016/j.adcanc.2025.100166

Rifat Aara , Neeha Sinai Borker , Jyothilakshmi Sajimon , Seemadri Subhadarshini , Snijesh VP , Vidya P. Nimbalkar , Manju Moorthy , Archana P. Thankamony , Athul Krishnan R , Mohit Kumar Jolly , Jyothi S. Prabhu , Radhika Nair

Metastatic breast cancer (mBC) remains an incurable disease with limited treatment options, highlighting the need for novel therapeutic approaches. The eventual development of resistance to commonly used regimens leading to relapse suggested the presence of intrinsically resistant heterogeneous cell populations. Our previous work identified heterogeneous metastatic tumor cell populations with distinct molecular characteristics driven by MACC1 (Metastasis Associated Colon Cancer 1), which is a key driver of metastasis and therapeutic resistance in multiple solid cancers, including breast cancer. We demonstrated that lovastatin (transcriptional inhibitor of MACC1) treatment ablated the metastatic cells through Macc1 downregulation. Building on this foundation, we evaluated the efficacy of lovastatin in lung metastases and elucidated its regulatory pathways in mBC.

Spatial transcriptomics on an Indian breast cancer patient cohort revealed heterogeneous MACC1 expression across tumors, which correlated with aggressive clinical features. Heterogeneous tumor cells [bulk tumor (Bulk), primary tumor (T1), lung-specific metastatic (L1) cells] were characterized from a metastatic murine model, with L1 showing the highest proliferation rate and MACC1 expression. Lovastatin treatment significantly downregulated MACC1 expression in L1 cells resulting in inhibition of key metastatic phenotypes like proliferation and migration, as well as altered cell type-specific gene expression of programmes like EMT and dormancy, with protein–ligand docking simulations with Sp1, indicating a potential transcriptional regulatory mechanism. Finally, we explored the therapeutic efficacy of lovastatin in combination with chemotherapy and demonstrated that lovastatin effectively ablated chemoresistant tumor cells in mBC. The translational implications of this research could identify patient subgroups that may benefit from statin–chemotherapy combinations and support the repurposing of statins as cost-effective adjuvant therapies for mBC.

转移性乳腺癌（mBC）仍然是一种无法治愈的疾病，治疗方案有限，强调需要新的治疗方法。对常用治疗方案的耐药性最终发展导致复发，这表明存在内在耐药的异质细胞群。我们之前的工作发现了由MACC1（转移相关结肠癌1）驱动的具有不同分子特征的异质性转移性肿瘤细胞群，MACC1是包括乳腺癌在内的多种实体癌转移和治疗耐药的关键驱动因素。我们证明洛伐他汀（MACC1转录抑制剂）治疗通过MACC1下调来消融转移细胞。在此基础上，我们评估了洛伐他汀在肺转移中的疗效，并阐明了其在mBC中的调控途径。一项印度乳腺癌患者队列的空间转录组学研究显示，MACC1在肿瘤中的表达存在异质性，这与侵袭性临床特征相关。异质性肿瘤细胞[散装肿瘤（bulk tumor），原发肿瘤（T1），肺特异性转移（L1）细胞]在转移小鼠模型中被表征，L1显示出最高的增殖率和MACC1表达。洛伐他汀治疗显著下调L1细胞中的MACC1表达，导致增殖和迁移等关键转移表型的抑制，以及EMT和休眠等细胞类型特异性基因表达的改变，通过与Sp1的蛋白配体对接模拟，表明潜在的转录调控机制。最后，我们探讨了洛伐他汀联合化疗的治疗效果，并证明洛伐他汀有效地消融了mBC中的化疗耐药肿瘤细胞。这项研究的转化意义可以确定可能受益于他汀类化疗联合的患者亚组，并支持他汀类药物作为成本效益高的mBC辅助治疗的重新用途。

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引用次数: 0

Anticancer efficacy of 2-Hydroxy-4-methoxybenzoic acid through dual regulation of lactate transport via inhibition of MCT-1 and MCT-4 2-羟基-4-甲氧基苯甲酸通过抑制MCT-1和MCT-4双重调节乳酸转运的抗癌作用

IF 3 Q3 ONCOLOGY

Advances in cancer biology - metastasis

Pub Date : 2025-11-18 DOI: 10.1016/j.adcanc.2025.100163

Sneha Yadav , Jyoti Singh , Rohit Kumar , Archana Bharti Sonkar , Anurag Kumar , Dharmendra Kumar , Neeraj Kumar Shrivastava , Mohd Nazam Ansari , Abdulaziz S. Saeedan , Sara A. Aldossary , Gaurav Kaithwas

Monocarboxylate transporters (MCTs) play critical role in the progression of mammary gland carcinoma. The unregulated cell growth increased glycolytic phenotype via glycolysis pathway which leads to concomitant synthesis of lactate. Lactate facilitates acidification of tumour microenvironment (TME), metastasis, and immune evasion. Thus, MCTs inhibition has emerged as a novel approach to treat mammary gland carcinoma. Herein, the current study aim to identify and validate small molecule as dual MCT-1 and MCT-4 inhibitor for mammary gland chemoprevention. We performed structure based virtual screening of natural based library (HY-L057L) and outcomes underscore 2-Hydroxy-4-methoxybenzoic acid (HMBA) as potential compound. HMBA demonstrated higher molecular docking score, favourable ADMET profiling and drug-likeness.Moreover, HMBA was examined for its cytotoxicity and apoptotic activity via in-vitro studies on MCF-7 cells. The results showed that HMBA possessed a substantial IC50 value of 4.8 μM and having apoptotic potential. Additionally, we tested its anticancer effects against a 7,12- dimethylbenz[a]anthracene) (DMBA)-induced tumour model in-vivo. Our findings demonstrated that the HMBA effectively corrected the altered histology and morphology. The altered levels of lactate and antioxidant were also restored by HMBA. In addition, HMBA regulate the mitochondrial apoptotic pathway and inhibit the hypoxia and angiogenesis and the lactate exchange transporters proteins, according to the results of the western blotting. The overall findings obtained from in-silico, in-vitro, and in-vivo studies present strong evidence for the pre-clinical effectiveness of HMBA in treating mammary gland carcinoma through dual inhibition of MCT-1 and MCT-4 and may pave the way for more Investigational New Drug (IND) compliance testing.

单羧酸转运蛋白（mct）在乳腺癌的进展中起着关键作用。不受调节的细胞生长通过糖酵解途径增加糖酵解表型，导致伴随的乳酸合成。乳酸促进肿瘤微环境（TME）酸化、转移和免疫逃逸。因此，抑制mct已成为治疗乳腺癌的一种新方法。本研究旨在鉴定和验证小分子作为MCT-1和MCT-4双重抑制剂在乳腺化学预防中的作用。我们对天然基文库（HY-L057L）进行了基于结构的虚拟筛选，结果表明2-羟基-4-甲氧基苯甲酸（HMBA）是潜在的化合物。HMBA表现出较高的分子对接评分、良好的ADMET谱和药物相似性。此外，通过MCF-7细胞的体外研究，研究了HMBA的细胞毒性和凋亡活性。结果表明，HMBA具有4.8 μM的IC50值，并具有凋亡潜能。此外，我们测试了其对7,12-二甲基苯[a]蒽)（DMBA）诱导的肿瘤模型的体内抗癌作用。我们的研究结果表明，HMBA有效地纠正了组织学和形态学的改变。HMBA也恢复了乳酸和抗氧化剂水平的改变。western blotting结果显示，HMBA调节线粒体凋亡通路，抑制缺氧、血管生成和乳酸交换转运蛋白。从计算机、体外和体内研究中获得的总体结果为HMBA通过双重抑制MCT-1和MCT-4治疗乳腺癌的临床前有效性提供了强有力的证据，并可能为更多的研究新药（IND）依从性测试铺平道路。

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引用次数: 0

Enhancing the anticancer effect of NAMPT inhibition by targeting NAPRT in breast cancer cells 通过靶向乳腺癌细胞的NAPRT增强NAMPT抑制的抗癌作用

IF 3 Q3 ONCOLOGY

Advances in cancer biology - metastasis

Pub Date : 2025-11-13 DOI: 10.1016/j.adcanc.2025.100161

Zahra Gharedaghi , Parichehr Mehrafshar , Soha Mohammadi , Masoumeh Tavakoli-Yaraki , Pegah Golpour , Mitra Nourbakhsh , Nima Taghizadeh

Introduction

Two pathways in the synthesis of NAD, catalyzed by the key enzymes nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase (NAPRT), support constant survival, growth, and propagation of cancer cells. This study investigated the effect of the NAMPT inhibitor FK866 combined with 2-Hydroxynicotinic Acid (2-HNA), an inhibitor of nicotinate phosphoribosyltransferase (NAPRT), on breast cancer cell survival, apoptosis, and metastasis.

Methods

MCF-7 and MDA-MB-231 breast cancer cells were cultured and treated with FK866, 2-HNA, or their combinations. Cell viability and apoptosis were evaluated using the MTT assay and Annexin V staining. The effect of inhibitors on p21, BAX, and p53 gene expression was assessed after RNA extraction and cDNA synthesis by real-time PCR using gene-specific primers. Cell migration and invasion were investigated using a scratch assay and matrigel penetration, respectively.

Results

The combination of inhibitors showed synergistic and additive effects in reducing cell viability in MCF-7 and MDA-MB-231 cells, respectively. Both inhibitors induced apoptosis and decreased invasion and migration in breast cancer cells; however, co-treatment was more effective than monotherapy. They significantly enhanced pro-apoptotic gene expression of p53, p21, and BAX, with co-treatment showing greater efficacy in both cell lines.

Conclusion

Simultaneous inhibition of NAMPT and NAPRT reduced cell viability, induced apoptosis, and inhibited metastasis of breast cancer cells. Therefore, targeting NAPRT in addition to NAMPT may offer a more effective therapeutic strategy for breast cancer.

NAD的合成有两种途径，由烟酰胺磷酸核糖基转移酶（NAMPT）和烟酸磷酸核糖基转移酶（NAPRT）两种关键酶催化，支持癌细胞的持续存活、生长和繁殖。本研究探讨了NAMPT抑制剂FK866联合烟酸磷酸核糖基转移酶（NAPRT）抑制剂2-羟基烟酸（2-HNA）对乳腺癌细胞存活、凋亡和转移的影响。方法培养smcf -7和MDA-MB-231乳腺癌细胞，用FK866、2-HNA或其组合处理。采用MTT法和Annexin V染色检测细胞活力和凋亡情况。利用基因特异性引物进行RNA提取和cDNA合成，评估抑制剂对p21、BAX和p53基因表达的影响。细胞迁移和侵袭分别采用划痕法和基质渗透法进行研究。结果联合用药对MCF-7细胞和MDA-MB-231细胞的细胞活力分别有增效和累加作用。两种抑制剂均可诱导乳腺癌细胞凋亡并减少其侵袭和迁移；然而，联合治疗比单一治疗更有效。它们显著增强了促凋亡基因p53、p21和BAX的表达，联合治疗在两种细胞系中显示出更大的疗效。结论同时抑制NAMPT和NAPRT可降低乳腺癌细胞活力，诱导细胞凋亡，抑制乳腺癌细胞转移。因此，除了靶向NAMPT外，靶向NAPRT可能为乳腺癌提供更有效的治疗策略。

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引用次数: 0

Hybrid EMT and inflammation: the deadly alliance 混合急救和炎症：致命的联盟

IF 3 Q3 ONCOLOGY

Advances in cancer biology - metastasis

Pub Date : 2025-10-29 DOI: 10.1016/j.adcanc.2025.100160

Rohit Gundamaraju , Vidhya Tangeda , Harshini Raja , Chandrashekar Goud , Hima Sree Buddiraju , Vishnu Pulavarthy

Tumors have unbounded components fitted which execute widespread pathophysiologies. It has been noted that tumor associated inflammation attributes to metastatic endpoints making it an aggressive phenotype. The inflammatory cells and system are set to have a cross talk with tumor cells in the microenvironment varying with the cancer. Likewise, EMT process might also trigger inflammation by the cancer cells. On the other hand, hybrid EMT possesses characteristics of both epithelial and mesenchymal nature which are said to possess unique stemness and express therapeutic resistance. A deeper understanding of the immune events in the tumor microenvironment is necessary to gain better understanding. Further, interpreting how cancer cells are attuning to stress and harsh environments is instrumental in learning about the concept of hybrid EMT. The current review focusses on the interrelationship between inflammation and how might aid in the hybrid EMT phenotype or the regulatory inflammatory factors bolstering hybrid EMT.

肿瘤具有无界的组成部分，这些组成部分执行广泛的病理生理。已经注意到，肿瘤相关的炎症归因于转移终点，使其成为一种侵袭性表型。炎症细胞和系统被设置在随癌症变化的微环境中与肿瘤细胞发生串扰。同样，EMT过程也可能引发癌细胞的炎症。另一方面，杂交EMT同时具有上皮和间充质性质，具有独特的干性和治疗抗性。深入了解肿瘤微环境中的免疫事件对于获得更好的理解是必要的。此外，解释癌细胞如何适应压力和恶劣环境有助于了解混合EMT的概念。目前的综述集中在炎症之间的相互关系以及如何帮助混合型EMT表型或调节炎症因子支持混合型EMT。

引用次数: 0

The multifaceted functions of lncRNA PTPRG-AS1 in human cancers: An in-depth investigation through extensive bioinformatic analyses and literature review lncRNA PTPRG-AS1在人类癌症中的多面功能：通过广泛的生物信息学分析和文献综述进行深入研究

IF 3 Q3 ONCOLOGY

Advances in cancer biology - metastasis

Pub Date : 2025-10-24 DOI: 10.1016/j.adcanc.2025.100159

Mohsen Ahmadi , Zahra Tajik , Kiana Salmani , Fatemeh Ghadyani , Soudeh Ghafouri-Fard

Long non-coding RNAs (lncRNAs) have important roles in gene regulation and disease pathogenesis. Among them, PTPRG-AS1 (Protein Tyrosine Phosphatase Receptor Type G Antisense RNA 1) has emerged as a potential player in several cancers, particularly breast cancer. This lncRNA has also been found to be over-expressed in nasopharyngeal carcinoma and lung cancer, among other cancers. Moreover, up-regulation of this lncRNA is associated with metastatic potential of gastric cancer, epithelial ovarian cancer, osteosarcoma, hepatocellular carcinoma and triple negative breast cancer. Several microRNAs have been reported as potential interacting molecules with PTPRG-AS1. This article explores the role of PTPRG-AS1 through a literature-based review and bioinformatics analysis, highlighting its molecular mechanisms, expression patterns, and clinical implications. The data summarized in this review may help design of novel anti-cancer therapies, particularly focusing on combating cancer hallmarks, such as stemness and invasion. However, further experimental validation is needed before implementation of these results in the clinical settings.

长链非编码rna （lncRNAs）在基因调控和疾病发病机制中具有重要作用。其中，PTPRG-AS1（蛋白酪氨酸磷酸酶受体G型反义RNA 1）已成为几种癌症，特别是乳腺癌的潜在参与者。这种lncRNA也被发现在鼻咽癌和肺癌等癌症中过度表达。此外，该lncRNA的上调与胃癌、上皮性卵巢癌、骨肉瘤、肝细胞癌和三阴性乳腺癌的转移潜能有关。一些microrna已被报道为可能与PTPRG-AS1相互作用的分子。本文通过文献综述和生物信息学分析探讨了PTPRG-AS1的作用，重点介绍了其分子机制、表达模式和临床意义。本综述总结的数据可能有助于设计新的抗癌疗法，特别是针对癌症特征，如干细胞和侵袭性。然而，在将这些结果应用于临床之前，还需要进一步的实验验证。

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引用次数: 0

The effect of acute and prolonged acidosis on a panel of carcinoma cell lines 急性和长期酸中毒对一组癌细胞系的影响

IF 3 Q3 ONCOLOGY

Advances in cancer biology - metastasis

Pub Date : 2025-10-22 DOI: 10.1016/j.adcanc.2025.100157

Maria Dravecka , Claire Wells , Ole Morten Seternes , Jakob Mejlvang

Due to cancer cell metabolism and disorganized tissue structure, the tumour microenvironment is associated with several pathophysiological conditions, including hypoxia, nutrient deprivation, accumulation of waste products, and acidification of the tumour microenvironment (tumour acidosis). Despite the belief that tumour acidosis drives tumorigenesis, it is still unclear how cancer cells respond to acidosis in the absence of other pathophysiological conditions. Here, we investigate how both acute and prolonged acidosis (pH 6.8) affects different epithelial features of a panel of carcinoma cell lines. We find that acute acidosis in all cell lines investigated represses cell growth and causes a disturbance of adherens junctions and apical-basal polarity, reminiscent of epithelial-to-mesenchymal transition (EMT). However, these changes did not coincide with altered expression of E− and N-cadherin. Neither did acute acidosis have a general effect on adhesion and migration in our panel of cell lines. Exposing our panel of carcinoma cell lines to acidosis for more than six weeks did not lead to adaptations restoring cell growth. On the contrary, prolonged acidosis caused one cell line (A431) to halt proliferation. Another cell line (A549) reacted to prolonged acidosis by gradually inducing the expression of ZEB2, which in turn orchestrated cadherin switching, possibly indicating a gradual induction of EMT. In the rest of the cell lines, we did not find any noticeable effect of prolonged acidosis. Lastly, all cell lines quickly restored their original phenotype and growth rate when returned to media with normal pH (pH 7.5). Collectively, our findings reveal that carcinoma cells exposed to moderate acidosis (pH 6.8) generally exhibit slower proliferation rates and a reduction in apical-basal polarity. Furthermore, we conclude that prolonged exposure to acidic conditions, depending on the specific cell line, may elicit responses that could influence tumour progression and the efficacy of cancer treatments.

由于癌细胞代谢和组织结构紊乱，肿瘤微环境与多种病理生理条件相关，包括缺氧、营养剥夺、废物积累和肿瘤微环境酸化（肿瘤酸中毒）。尽管认为肿瘤酸中毒驱动肿瘤发生，但在没有其他病理生理条件的情况下，癌细胞如何对酸中毒作出反应尚不清楚。在这里，我们研究了急性和长期酸中毒（pH值6.8）如何影响一组癌细胞系的不同上皮特征。我们发现，在所有被研究的细胞系中，急性酸中毒抑制细胞生长，并引起粘附连接和顶基极性的干扰，使人想起上皮到间充质转化（EMT）。然而，这些变化与E -和n -钙粘蛋白表达的改变并不一致。急性酸中毒对我们的细胞系的粘附和迁移也没有普遍的影响。将我们的癌细胞组暴露在酸中毒中超过六周并没有导致细胞恢复生长的适应性。相反，长时间的酸中毒导致一个细胞系（A431）停止增殖。另一种细胞系（A549）通过逐渐诱导ZEB2的表达来应对长时间的酸中毒，ZEB2反过来又协调钙粘蛋白的转换，可能表明逐渐诱导EMT。在其余的细胞系中，我们没有发现任何明显的长时间酸中毒的影响。最后，当返回正常pH （pH 7.5）培养基时，所有细胞系迅速恢复其原始表型和生长速度。总的来说，我们的研究结果表明，暴露于中度酸中毒（pH 6.8）的癌细胞通常表现出较慢的增殖速率和根尖极性的降低。此外，我们得出结论，长期暴露于酸性条件下，取决于特定的细胞系，可能引发可能影响肿瘤进展和癌症治疗效果的反应。

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引用次数: 0