Colorectal carcinoma cell production of transforming growth factor beta decreases expression of endothelial cell

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Updated: May 31, 2026

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
07:49

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

Elizabeth A Kuczynski1, Alicia M Viloria-Petit, Brenda L Coomber

  • 1Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada.

Cancer
|June 22, 2011
PubMed
Abstract

Insights

Transforming growth factor beta (TGF-β) down-regulates vascular endothelial growth factor receptor 2 (VEGFR2) in colorectal cancer (CRC) cells. This finding may explain vascular heterogeneity in CRC tumors, impacting antiangiogenic therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Vascular endothelial growth factor (VEGF) signaling is a key target for antiangiogenic cancer therapies.
  • A significant portion of vessels in colorectal carcinoma (CRC) tumors exhibit low or absent VEGF receptor 2 (VEGFR2) expression.
  • Transforming growth factor beta (TGF-β) activity is implicated in both angiogenesis and CRC progression, potentially contributing to VEGFR2 heterogeneity.

Purpose of the Study:

  • To investigate the role of TGF-β in regulating VEGFR2 expression in the context of colorectal cancer.
  • To determine if TGF-β contributes to the observed VEGFR2 heterogeneity in tumor vasculature.

Main Methods:

  • Western blotting was used to analyze VEGFR2 expression in endothelial and CRC cell lines.
  • TGF-β expression was quantified in CRC cell lines.
  • Immunofluorescence staining of CRC xenografts was performed to correlate VEGFR2 and TGF-β levels.
  • Inhibitors of TGF-β receptor I (SB-431542 and SD-208) were utilized.

Main Results:

  • TGF-β1 significantly repressed VEGFR2 protein expression in a time- and dose-dependent manner in bovine aortic endothelial cells (BAECs).
  • Conditioned media from human CRC cell lines down-regulated VEGFR2 in BAECs, an effect proportional to TGF-β1 and TGF-β2 levels and blocked by TGF-β receptor I inhibitors.
  • In vivo studies showed an inverse relationship between TGF-β activity and VEGFR2 expression in tumor vessels.
  • Oxygen and bone morphogenetic protein 9 levels were identified as modulators of TGF-β-induced VEGFR2 down-regulation.

Conclusions:

  • TGF-β plays a significant role in down-regulating VEGFR2 expression in endothelial cells.
  • This TGF-β-mediated suppression of VEGFR2 may contribute to the vascular heterogeneity observed in human colorectal tumors.
  • Understanding this mechanism is crucial for optimizing antiangiogenic therapies targeting VEGF signaling in CRC.

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