Elevated expression of angiomodulin (AGM/IGFBP-rP1) in tumor stroma and its roles in fibroblast activation

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A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
06:35

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth

Published on: December 22, 2020

Eriko Komiya1, Momoko Furuya, Naoko Watanabe

  • 1Graduate School of Integrated Sciences, Yokohama City University, Yokohama, Japan.

Cancer Science
|February 11, 2012
PubMed

Insights

Angiomodulin (AGM) activates normal fibroblasts, promoting tumor progression. This glycoprotein stimulates fibroblast proliferation and migration, potentially through transforming growth factor-beta (TGF-β)-dependent and independent pathways, contributing to cancer stroma formation.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Angiomodulin (AGM/IGFBP-rP1) is a glycoprotein implicated in tumor biology.
  • AGM is overexpressed in tumor vasculature and some cancer cell lines.
  • Its role as a tumor suppressor has been debated, necessitating further investigation into its function in tumor progression.

Purpose of the Study:

  • To investigate the distribution and role of angiomodulin (AGM) in human cancer tissues.
  • To elucidate the mechanisms by which AGM influences fibroblast activation and tumor stroma formation.

Main Methods:

  • Immunohistochemistry was used to examine AGM distribution in three types of human cancer tissues.
  • In vitro studies analyzed the effects of AGM on normal human fibroblasts, including proliferation, migration, and gene expression.
  • Transforming growth factor-beta (TGF-β) signaling inhibitors were employed to dissect signaling pathways.

Main Results:

  • AGM was found to be overexpressed in the stroma and vasculature surrounding tumor cells.
  • AGM colocalized with alpha-smooth muscle actin (α-SMA), a marker for cancer-associated fibroblasts (CAFs).
  • AGM stimulated fibroblast proliferation and migration, and induced fibronectin and α-SMA expression, partly via TGF-β-dependent pathways.

Conclusions:

  • AGM activates normal fibroblasts through both TGF-β-dependent and independent mechanisms.
  • AGM and TGF-β1 may cooperatively contribute to stromal activation and connective tissue formation in human cancers.
  • These findings suggest AGM plays a role in promoting tumor progression via stromal modulation.

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