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In vitro Organoid Culture of Primary Mouse Colon Tumors
07:33

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Published on: May 17, 2013

The bone morphogenetic protein pathway is active in human colon adenomas and inactivated in colorectal cancer

Liudmila L Kodach1, Sylvia A Bleuming, Alex R Musler

  • 1Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.

Cancer
|November 17, 2007
PubMed
Abstract

Insights

Loss of bone morphogenetic protein (BMP) signaling is strongly linked to colorectal cancer (CRC) progression. This critical BMP signaling loss occurs early, during the transition from adenomas to CRC, indicating its importance in cancer development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gastroenterology

Background:

  • Transforming growth factor beta (TGFbeta) superfamily plays a role in colorectal cancer (CRC) progression.
  • Bone morphogenetic proteins (BMPs), a subgroup of TGFbeta, are implicated in CRC, but their specific function remains unclear.

Purpose of the Study:

  • To investigate the role of BMP signaling in colorectal cancer (CRC) carcinogenesis.
  • To elucidate the expression and activity of BMP receptors and signaling pathways in adenomas and CRC.

Main Methods:

  • Utilized a tissue microarray and immunohistochemistry on adenoma and CRC specimens.
  • Assessed the expression of BMP receptors (BMPR1a, BMPR1b, BMPR2) and SMAD4.
  • Determined active BMP signaling via nuclear phosphorylated SMAD1,5,8 (pSMAD1,5,8) expression.

Main Results:

  • Adenomas showed high expression of BMP receptors and SMAD4, with 90.9% exhibiting active BMP signaling (nuclear pSMAD1,5,8).
  • Colorectal cancer (CRC) specimens displayed significantly reduced active BMP signaling (22.7% vs 90.9%; P< .0001).
  • Loss of BMP signaling was detected early in high-grade dysplasia/carcinoma in situ. Frequent loss of BMPR2 and SMAD4 was observed in CRCs compared to adenomas.

Conclusions:

  • Loss of BMP signaling is tightly correlated with the progression from adenomas to colorectal cancer (CRC).
  • The disruption of BMP signaling appears to be an early event in colorectal cancer (CRC) progression.

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