Whom to blame for metastasis, the epithelial-mesenchymal transition or the tumor microenvironment?

Cancer Letters
M PietiläSendurai A Mani

Abstract

Changes in the tumor microenvironment (TME) can trigger the activation of otherwise non-malignant cells to become highly aggressive and motile. This is evident during initial tumor growth when the poor vascularization in tumors generates hypoxic regions that trigger the latent embryonic program, epithelial-to-mesenchymal transition (EMT), in epithelial carcinoma cells (e-cars) leading to highly motile mesenchymal-like carcinoma cells (m-cars), which also acquire cancer stem cell properties. After that, specific bidirectional interactions take place between m-cars and the cellular components of TME at different stages of metastasis. These interactions include several vicious positive feedback loops in which m-cars trigger a phenotypic switch, causing normal stromal cells to become pro-tumorigenic, which then further promote the survival, motility, and proliferation of m-cars. Accordingly, there is not a single culprit accounting for metastasis. Instead both m-cars and the TME dynamically interact, evolve and promote metastasis. In this review, we discuss the current status of the known interactions between m-cars and the TME during different stages of metastasis and how these interactions promote the metastatic activity of highl...Continue Reading

References

Sep 1, 1992·NMR in Biomedicine·P Vaupel
Aug 1, 1995·The Journal of Experimental Medicine·M F Krummel, J P Allison
Aug 1, 1994·Immunity·T L WalunasJ A Bluestone
May 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·G L Wang, G L Semenza
Sep 17, 1999·The American Journal of Pathology·A J ManiotisM J Hendrix
Feb 10, 2000·The American Journal of Pathology·R FolbergA J Maniotis
Feb 22, 2001·Journal of the National Cancer Institute·M Höckel, P Vaupel
Jun 13, 2003·Molecular Biology of the Cell·Richard C Bates, Arthur M Mercurio
Dec 11, 2003·Proceedings of the National Academy of Sciences of the United States of America·Britta WeigeltLaura J van't Veer
Mar 18, 2005·Annual Review of Immunology·Rebecca J GreenwaldArlene H Sharpe
Dec 17, 2005·Cancer Research·Daisy W J van der SchaftArjan W Griffioen
Sep 9, 2006·Science·Tobias SjöblomVictor E Velculescu
Jan 5, 2008·Annual Review of Immunology·Mary E KeirArlene H Sharpe
Jan 8, 2008·Cell Metabolism·Ralph J DeBerardinisCraig B Thompson
Feb 5, 2008·Cancer Research·Neil H SegalJames P Allison
Feb 21, 2008·PloS One·Rulong ShenJian-Xin Gao
Feb 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·F Stephen HodiGlenn Dranoff
Feb 26, 2008·Nature Cell Biology·Muh-Hwa YangKou-Juey Wu
Apr 16, 2008·Journal of Cellular and Molecular Medicine·Benedetta BussolatiGiovanni Camussi
May 24, 2008·Molecular Cell·William G Kaelin, Peter J Ratcliffe
Aug 7, 2008·PloS One·Anne-Pierre MorelAlain Puisieux
Dec 4, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tao SunBao-Cun Sun
Feb 18, 2010·International Journal of Cancer. Journal International Du Cancer·Candice A ShaiferPengnain Charles Lin
May 13, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Bradley C CarthonPadmanee Sharma
Aug 11, 2010·Stem Cell Reviews and Reports·Jun DongXiaosong Gu
Nov 26, 2010·Cancer Research·Jason WebberAled Clayton
Nov 26, 2010·Cancer Research·Sudha KrishnamurthyJacques E Nör
Jan 20, 2011·Cancer Research·Panagiotis PapageorgisSam Thiagalingam
Jan 26, 2011·Proceedings of the National Academy of Sciences of the United States of America·Yasushi SodaInder M Verma
May 3, 2011·Protein & Cell·Xiao-hong YaoXiu-wu Bian
May 5, 2011·Biochemical and Biophysical Research Communications·Jin-lu MaYi Lv
Aug 13, 2011·The New England Journal of Medicine·Gregg L Semenza
Sep 6, 2011·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Yvonne ChaoAlan Wells

❮ Previous
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Citations

Mar 5, 2016·Journal of Experimental & Clinical Cancer Research : CR·Emmanuel ZervosRachel L Roper
Aug 1, 2016·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Martin WartenbergEva Karamitopoulou
Nov 8, 2017·International Journal of Molecular Sciences·Ana CavacoJohannes A Eble
Apr 12, 2019·Clinical & Experimental Metastasis·Johannes A Eble, Stephan Niland
Aug 8, 2020·International Journal of Cancer. Journal International Du Cancer·Sivan Izraely, Isaac P Witz
Jan 31, 2017·Annual Review of Pathology·J-A ThieleP Kuhn
Sep 29, 2018·F1000Research·Jessica L ChittyPaul Timpson
Dec 28, 2018·Proceedings of the National Academy of Sciences of the United States of America·Federico BocciMohit Kumar Jolly
Jan 5, 2020·Journal of Translational Medicine·Bernardo Cacho-DíazLuis Alonso Herrera-Montalvo
Nov 21, 2018·Frontiers in Oncology·Xiao YangYaling Tang
Sep 21, 2018·American Society of Clinical Oncology Educational Book·Xiaoliang WuPatrick C Ma
Apr 15, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ila Datar, Kurt A Schalper
Jan 12, 2020·Experimental Cell Research·Xiaoying GuanZuoyi Jiao
Jul 13, 2018·Biochimica Et Biophysica Acta. Reviews on Cancer·Mohit Kumar JollyHerbert Levine
May 4, 2020·The American Journal of Pathology·Tomomi Yamamoto-FukudaHiromi Kojima

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