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BMP4/Thrombospondin-1 loop paracrinically inhibits tumor angiogenesis and suppresses the growth of solid tumors

R Tsuchida1, T Osawa2, F Wang3

  • 11] Department of Molecular Oncology, Tokyo Medical and Dental University, Tokyo, Japan [2] Department of Pediatrics, Tokyo Medical and Dental University, 1-5-45 Yushima, Tokyo, Japan.

Oncogene
|September 10, 2013
PubMed

Insights

Bone morphogenetic protein 4 (BMP4) inhibits tumor growth by reducing blood vessel formation. This anticancer agent induces Thrombospondin-1 (TSP1), suppressing tumor angiogenesis and offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Bone morphogenetic protein 4 (BMP4) shows promise as an anticancer agent.
  • Previous research indicates BMP4 inhibits cancer stem cells (CSCs) in neural and colon cancers.

Purpose of the Study:

  • To investigate the mechanism by which BMP4 suppresses tumor growth.
  • To explore BMP4's role in tumor angiogenesis and its potential as an antiangiogenic therapy.

Main Methods:

  • Assessing BMP4's effect on tumor growth in vivo using HeLa, HCI-H460-LNM35, and B16 cancer cell xenografts.
  • Measuring mRNA expression of angiogenesis-related factors, including Thrombospondin-1 (TSP1) and vascular endothelial growth factor (VEGF).
  • Evaluating tumor growth in TSP1-knockdown cancer cells treated with BMP4.

Main Results:

  • BMP4 administration suppressed tumor growth in vivo by inhibiting tumor angiogenesis, despite cancer cells not responding in vitro.
  • BMP4 significantly upregulated TSP1 mRNA expression in grafted tumors.
  • BMP4 reduced VEGF expression in a TSP1-dependent manner, interfering with tumor angiogenesis stabilization.
  • BMP4's tumor growth suppression was less effective in TSP1-knockdown cancer cells.

Conclusions:

  • The BMP4/TSP1 signaling pathway plays a crucial role in paracrinely suppressing tumor angiogenesis within the tumor microenvironment.
  • BMP4 effectively reduces tumor growth by inhibiting angiogenesis through TSP1 induction.
  • BMP4 represents a potential novel antitumor agent and a new avenue for antiangiogenic therapy.

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