Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

Overxpression of Angiomodulin (AGM/IGFBP-rP1) in Tumor Stroma and Vasculature: Differential Regulation and Functions. (#174)

Eriko Komiya 1 , Hiroki Sato 1 , Shouichi Higashi 1 , Yohei Miyagi 2 , Kaoru Miyazaki 1
  1. Division of Cell Biology, Yokohama-city University, Yokohama-city, Japan
  2. Devision of Cancr Therapy, Kanagawa Cancer Center Reseach Institute, Yokohama-city, Japan

Angiomodulin (AGM/IGFBP-rP1) is a member of IGFBP superfamily. We previously reported that AGM is highly accumulated in blood vessels of human cancer tissues. Contradictory results have been reported with respect to the roles of AGM in tumor progression. To elucidate its roles in tumor growth, we analyzed the distribution of AGM in four major types of human cancers by immunohistochemistry in detail. In colon, lung, uterus and breast cancers, AGM was overexpressed in stromal fibroblasts as well as in vasculature near tumor cells, but its expression in tumor cells was evident only in a few cases of cancers. AGM expression in stromal fibroblasts was often colocalized with alpha-smooth muscle actin (SMA), an activated fibroblast (myofibroblast) marker. These results suggested that AGM may play some roles in cancer-associated fibroblasts (CAFs). Among different stages of breast cancers, AGM was highly overexpressed in vasculature even in benign tumors (DCIS), while its expression in fibroblasts was more prominent in invasive carcinomas than DCIS. AGM was induced by TGF-beta in fibroblasts but by VEGF in endothelial cells. In vitro analyses showed that AGM stimulated strongly the expression of fibronectin and weakly that of SMA in normal fibroblasts and induced their morphological change to a myofibroblast-like shape. AGM also significantly stimulated the proliferation of fibroblasts. The induction of protein expression and morphological change were blocked by TGF-beta signal inhibitor, but its growth activity was not. On the other hand, AGM did not stimulate the growth of human umbilical endothelial cells (HUVEC). However, it significantly promoted their adhesion through integrins. These results indicate that AGM is overexpressed by different mechanisms and exerts different functions between stromal fibroblasts and endothelial cells in tumor tissues. It is supposed that such expression and activities of AGM contribute to tumor progression.

  1. Komiya E., et al. Elevated expression of angiomodulin (AGM/IGFBP-rP1) in tumor stroma and its roles in fibroblast activation. Cancer Sci 4: 691-9, 2012.