Differential impact of TGF-beta and EGF on fibroblast differentiation and invasion reciprocally promotes colon cancer cell invasion

Cancer Letters
Hannelore DenysOlivier De Wever

Abstract

Several studies indicate that cancer-associated fibroblasts play a critical role in cancer cell invasion and metastasis, the hallmarks of malignancy. To better understand the mechanisms underlying such effects, we established a heterotypic model of human fibroblasts (primary colon fibroblasts and immortalized human dermal fibroblasts) in co-culture with human colon cancer cells (HCT-8/E11), using three-dimensional collagen type-I and Matrigel matrices. We report that TGF-beta is the unique and dominant factor to provide pro-invasive signals to HCT-8/E11 colon cancer cells from TGF-beta-treated human fibroblasts in three-dimensional collagen type I and Matrigel matrices. These effects are not mimicked or reversed by EGF or bFGF, and are associated with the TGF-beta-mediated induction of myofibroblast differentiation and functional markers, such as alpha-SMA, the haptotactic matrix molecule TNC, collagen type 1 maturation enzyme P4H, serine protease FAP, and myofibroblast contractility. Accordingly, TGF-beta induced a strong activation of RhoA and stress fiber formation in fibroblasts, with no impact on Rac1-GTP levels. In contrast, EGF down-regulated Rho-GTP levels in fibroblasts, giving permissive signals for Rac1 activation, f...Continue Reading

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Citations

Jul 24, 2008·Histochemistry and Cell Biology·Olivier De WeverGeert Berx
Jan 11, 2014·Seminars in Cancer Biology·Olivier De WeverMarc Bracke
Oct 8, 2011·International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists·Jian-Jun WeiSerdar Bulun
Apr 7, 2012·International Journal of Breast Cancer·Zahraa I KhamisQing-Xiang Amy Sang
Apr 8, 2011·American Journal of Respiratory and Critical Care Medicine·Jennifer L IngramMonica Kraft
Aug 12, 2015·Virchows Archiv : an International Journal of Pathology·Elly De VlieghereOlivier De Wever
Mar 19, 2009·Orvosi hetilap·Gábor ValczZsolt Tulassay
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Jan 25, 2017·Cancers·Damien A Leach, Grant Buchanan
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Aug 26, 2011·International Journal of Cancer. Journal International Du Cancer·Ole Didrik LaerumMartin Illemann
May 28, 2009·Virchows Archiv : an International Journal of Pathology·Marc MareelIndira Madani
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Jun 30, 2021·Journal of Experimental & Clinical Cancer Research : CR·Pablo Hernández-CamareroMacarena Perán
Oct 1, 2021·Future Medicinal Chemistry·Ashutosh SinghNeha Garg

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