Pub Date : 2018-08-01DOI: 10.1158/1557-3265.OVCA17-A35
F. Qian, J. Liao, A. Miliotto, Katherine A. Collins, K. Odunsi
{"title":"Abstract A35: Ovarian cancer stem cells subvert tumor-specific T cells by disrupting T cells’ metabolic fitness","authors":"F. Qian, J. Liao, A. Miliotto, Katherine A. Collins, K. Odunsi","doi":"10.1158/1557-3265.OVCA17-A35","DOIUrl":"https://doi.org/10.1158/1557-3265.OVCA17-A35","url":null,"abstract":"","PeriodicalId":18646,"journal":{"name":"Metabolic Changes in Ovarian Cancer","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84658469","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}
Pub Date : 2018-08-01DOI: 10.1158/1557-3265.OVCA17-A12
Adrian V Buensuceso, Yudith Ramos Valdés, R. Figueredo, G. DiMattia, T. Shepherd
{"title":"Abstract A12: The metabolic stress mediator LKB1 is required for ovarian cancer metastasis","authors":"Adrian V Buensuceso, Yudith Ramos Valdés, R. Figueredo, G. DiMattia, T. Shepherd","doi":"10.1158/1557-3265.OVCA17-A12","DOIUrl":"https://doi.org/10.1158/1557-3265.OVCA17-A12","url":null,"abstract":"","PeriodicalId":18646,"journal":{"name":"Metabolic Changes in Ovarian Cancer","volume":"11 6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78798789","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}
Pub Date : 2018-08-01DOI: 10.1158/1557-3265.OVCA17-A54
J. Hoare, J. Saxena, H. Hockings, J. McDermott, Ashley K. Browne, M. Lockley
{"title":"Abstract A54: Generation and characterization of a novel panel of platinum-resistant HGSOC models","authors":"J. Hoare, J. Saxena, H. Hockings, J. McDermott, Ashley K. Browne, M. Lockley","doi":"10.1158/1557-3265.OVCA17-A54","DOIUrl":"https://doi.org/10.1158/1557-3265.OVCA17-A54","url":null,"abstract":"","PeriodicalId":18646,"journal":{"name":"Metabolic Changes in Ovarian Cancer","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74732557","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}
Pub Date : 2018-08-01DOI: 10.1158/1557-3265.OVCA17-A52
Daniela F. Fukushiro-Lopes, M. Jain, Maryam Khalid, A. Hegel, S. Gentile
{"title":"Abstract A52: Potassium channel activator minoxidil (Rogaine) as a novel single-agent or combination therapy in ovarian cancer","authors":"Daniela F. Fukushiro-Lopes, M. Jain, Maryam Khalid, A. Hegel, S. Gentile","doi":"10.1158/1557-3265.OVCA17-A52","DOIUrl":"https://doi.org/10.1158/1557-3265.OVCA17-A52","url":null,"abstract":"","PeriodicalId":18646,"journal":{"name":"Metabolic Changes in Ovarian Cancer","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88274019","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}
Pub Date : 2018-08-01DOI: 10.1158/1557-3265.OVCA17-A18
O. Zeleznik, E. Poole, C. Clish, H. Eliassen, P. Kraft, S. Tworoger
{"title":"Abstract A18: Metabolomic analysis of ovarian cancer risk in the Nurses’ Health Studies: Metabolite associations are more pronounced in non-serous tumors","authors":"O. Zeleznik, E. Poole, C. Clish, H. Eliassen, P. Kraft, S. Tworoger","doi":"10.1158/1557-3265.OVCA17-A18","DOIUrl":"https://doi.org/10.1158/1557-3265.OVCA17-A18","url":null,"abstract":"","PeriodicalId":18646,"journal":{"name":"Metabolic Changes in Ovarian Cancer","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81084123","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}
Pub Date : 2018-08-01DOI: 10.1158/1557-3265.OVCA17-PR04
A. Amobi, T. Tsuji, R. Mcgray, K. Odunsi
{"title":"Abstract PR04: Tumor-derived indoleamine 2,3-dioxygenase regulates density of tumor-infiltrating CD8+ T cells and myeloid-derived suppressor cells in a murine model of ovarian cancer","authors":"A. Amobi, T. Tsuji, R. Mcgray, K. Odunsi","doi":"10.1158/1557-3265.OVCA17-PR04","DOIUrl":"https://doi.org/10.1158/1557-3265.OVCA17-PR04","url":null,"abstract":"","PeriodicalId":18646,"journal":{"name":"Metabolic Changes in Ovarian Cancer","volume":"266 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91537956","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}
Pub Date : 2018-08-01DOI: 10.1158/1557-3265.OVCA17-A34
S. Tomar, J. Plotnik, James Haley, Joshua Scantland, Zahir Sheikh, R. Emerson, D. Lenz, Peter C. Hollenhorst, A. Mitra
Metastatic colonization of ovarian cancer involves productive paracrine/juxtacrine interactions with the microenvironment. The resulting induction of an adaptive response in the cancer cells enables them to establish themselves in the new microenvironment and take advantage of the new factors available. A key feature of this adaptation is induced changes in gene expression through transcriptional regulation as a result of microenvironmental cues. However, the identities of transcription factors induced by the metastatic microenvironment in ovarian cancer and their mechanism of action are poorly understood. Using an organotypic 3D culture model recapitulating the early events of metastasis, we identified ETS1, a member of the ETS family of TFs, as an essential driver of metastatic colonization. Increased ETS1 expression was induced in metastasizing ovarian cancer cells interacting with the mesothelial cells covering the surface of the omentum. The mechanism of upregulation was through the activation of p44/42 MAP kinase signaling in the cancer cells induced by TGFbeta from the microenvironment. We also found an increased ETS1 expression in human ovarian cancer samples as compared to normal fallopian tubes using a tissue microarray. Moreover, higher expression of ETS1 was a predictor of poor prognosis in ovarian cancer patients. Knocking down ETS1 decreased migration, proliferation, and colony formation as well as invasion through and colonization of the organotypic 3D culture. Overexpression of ETS1 had the opposite effect. CRISPR/Cas9-mediated knockout of ETS1 resulted in decreased tumor burden in mouse xenografts. A combination of ChIP-seq and RNA-seq analysis revealed that ETS1 promoted an EMT phenotype and FAK was identified as a novel transcriptional target. Inhibition of FAK functionally mimicked the effects of ETS1 inhibition in the ovarian cancer cells. Moreover, functional rescue experiments established FAK as a downstream effector of ETS1 during ovarian cancer metastasis. Taken together, our results indicate that ETS1 is an essential transcription factor induced in ovarian cancer cells by the microenvironment, which promotes metastatic colonization. This is the first report establishing FAK as a transcriptional target and functional effector of ETS1 in establishing metastatic tumors. Citation Format: Sunil Tomar, Joshua P. Plotnik, James Haley, Joshua Scantland, Zahir Sheikh, Robert Emerson, Dean Lenz, Peter C. Hollenhorst, Anirban K. Mitra. Induction of a novel ETS1/FAK pathway in metastasizing ovarian cancer cells by the omental microenvironment primes them for metastatic colonization. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr A34.
卵巢癌的转移性定植涉及与微环境的生产性旁分泌/近分泌相互作用。由此产生的癌细胞适应性反应的诱导使它们能够在新的微环境中建立自己，并利用新的可用因素。这种适应的一个关键特征是由于微环境线索通过转录调控诱导基因表达的变化。然而，卵巢癌转移微环境诱导的转录因子的特性及其作用机制尚不清楚。通过一个器官型3D培养模型，我们发现ETS1是转移的重要驱动因素，ETS1是TFs ETS家族的一员。与网膜表面间皮细胞相互作用的转移性卵巢癌细胞诱导ETS1表达增加。其上调机制是通过微环境中tgf β诱导癌细胞激活p44/42 MAP激酶信号。我们还发现，与正常输卵管相比，人类卵巢癌样本中ETS1的表达增加。此外，ETS1的高表达是卵巢癌患者预后不良的预测因子。敲除ETS1降低了器官型3D培养物的迁移、增殖、集落形成以及入侵和定植。过表达ETS1则有相反的效果。CRISPR/ cas9介导的敲除ETS1可降低小鼠异种移植物的肿瘤负荷。ChIP-seq和RNA-seq分析的结合显示，ETS1促进了EMT表型，而FAK被确定为新的转录靶点。FAK的抑制在功能上模仿了卵巢癌细胞中ETS1的抑制作用。此外，功能修复实验证实FAK是卵巢癌转移过程中ETS1的下游效应因子。综上所述，我们的研究结果表明，ETS1是微环境诱导卵巢癌细胞中促进转移定植的重要转录因子。这是首次证实FAK是ETS1在转移性肿瘤形成中的转录靶点和功能效应因子。引文格式:Sunil Tomar, Joshua P. Plotnik, James Haley, Joshua Scantland, Zahir Sheikh, Robert Emerson, Dean Lenz, Peter C. Hollenhorst, Anirban K. Mitra通过网膜微环境诱导转移性卵巢癌细胞的新型ETS1/FAK通路，为转移性定植提供了条件。[摘要]。AACR会议论文集:解决卵巢癌研究和治疗中的关键问题;2017年10月1-4日;宾夕法尼亚州匹兹堡。费城(PA): AACR;临床肿瘤杂志，2018;24(15 -增刊):摘要nr A34。
{"title":"Abstract A34: Induction of a novel ETS1/FAK pathway in metastasizing ovarian cancer cells by the omental microenvironment primes them for metastatic colonization","authors":"S. Tomar, J. Plotnik, James Haley, Joshua Scantland, Zahir Sheikh, R. Emerson, D. Lenz, Peter C. Hollenhorst, A. Mitra","doi":"10.1158/1557-3265.OVCA17-A34","DOIUrl":"https://doi.org/10.1158/1557-3265.OVCA17-A34","url":null,"abstract":"Metastatic colonization of ovarian cancer involves productive paracrine/juxtacrine interactions with the microenvironment. The resulting induction of an adaptive response in the cancer cells enables them to establish themselves in the new microenvironment and take advantage of the new factors available. A key feature of this adaptation is induced changes in gene expression through transcriptional regulation as a result of microenvironmental cues. However, the identities of transcription factors induced by the metastatic microenvironment in ovarian cancer and their mechanism of action are poorly understood. Using an organotypic 3D culture model recapitulating the early events of metastasis, we identified ETS1, a member of the ETS family of TFs, as an essential driver of metastatic colonization. Increased ETS1 expression was induced in metastasizing ovarian cancer cells interacting with the mesothelial cells covering the surface of the omentum. The mechanism of upregulation was through the activation of p44/42 MAP kinase signaling in the cancer cells induced by TGFbeta from the microenvironment. We also found an increased ETS1 expression in human ovarian cancer samples as compared to normal fallopian tubes using a tissue microarray. Moreover, higher expression of ETS1 was a predictor of poor prognosis in ovarian cancer patients. Knocking down ETS1 decreased migration, proliferation, and colony formation as well as invasion through and colonization of the organotypic 3D culture. Overexpression of ETS1 had the opposite effect. CRISPR/Cas9-mediated knockout of ETS1 resulted in decreased tumor burden in mouse xenografts. A combination of ChIP-seq and RNA-seq analysis revealed that ETS1 promoted an EMT phenotype and FAK was identified as a novel transcriptional target. Inhibition of FAK functionally mimicked the effects of ETS1 inhibition in the ovarian cancer cells. Moreover, functional rescue experiments established FAK as a downstream effector of ETS1 during ovarian cancer metastasis. Taken together, our results indicate that ETS1 is an essential transcription factor induced in ovarian cancer cells by the microenvironment, which promotes metastatic colonization. This is the first report establishing FAK as a transcriptional target and functional effector of ETS1 in establishing metastatic tumors. Citation Format: Sunil Tomar, Joshua P. Plotnik, James Haley, Joshua Scantland, Zahir Sheikh, Robert Emerson, Dean Lenz, Peter C. Hollenhorst, Anirban K. Mitra. Induction of a novel ETS1/FAK pathway in metastasizing ovarian cancer cells by the omental microenvironment primes them for metastatic colonization. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr A34.","PeriodicalId":18646,"journal":{"name":"Metabolic Changes in Ovarian Cancer","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83572841","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}
Pub Date : 2018-08-01DOI: 10.1158/1557-3265.ovca17-a21
M. J. Carroll, Kaitlin C. Fogg, H. A. Patel, A. Mancha, M. Patankar, P. Kreeger
{"title":"Abstract A21: Computational methods and novel in vitro model elucidate a therapeutic target against ovarian cancer metastasis","authors":"M. J. Carroll, Kaitlin C. Fogg, H. A. Patel, A. Mancha, M. Patankar, P. Kreeger","doi":"10.1158/1557-3265.ovca17-a21","DOIUrl":"https://doi.org/10.1158/1557-3265.ovca17-a21","url":null,"abstract":"","PeriodicalId":18646,"journal":{"name":"Metabolic Changes in Ovarian Cancer","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89167462","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}
Pub Date : 2018-08-01DOI: 10.1158/1557-3265.OVCA17-A31
L. Lecker, C. Trevisan, R. Delaine-Smith, E. Maniati, O. Pearce, C. Meinert, Marcin P Iwanicki, R. Drapkin, D. Loessner, F. Balkwill
{"title":"Abstract A31: Mutant p53 increases integrin-ECM interactions in early HGSOC","authors":"L. Lecker, C. Trevisan, R. Delaine-Smith, E. Maniati, O. Pearce, C. Meinert, Marcin P Iwanicki, R. Drapkin, D. Loessner, F. Balkwill","doi":"10.1158/1557-3265.OVCA17-A31","DOIUrl":"https://doi.org/10.1158/1557-3265.OVCA17-A31","url":null,"abstract":"","PeriodicalId":18646,"journal":{"name":"Metabolic Changes in Ovarian Cancer","volume":"137 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89760625","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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