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Cancer Sci. 2007 Jul;98(7):1055-63. Epub 2007 Apr 24.

Strong suppression of tumor growth by insulin-like growth factor-binding protein-related protein 1/tumor-derived cell adhesion factor/mac25.

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1
Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, 641-12 Maioka-cho, Totsuka-ku, Yokohama 244-0813, Japan.

Abstract

Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) has been shown to induce cellular senescence or apoptosis of breast and prostate cancer cell lines in vitro. To examine whether IGFBP-rP1 acts as a tumor-suppressive protein in vivo, we established two model systems. Expression of IGFBP-rP1 in the human bladder carcinoma cell line EJ-1 was blocked by RNA interference. Human colon cancer cell line DLD-1, which did not express endogenous IGFBP-rP1, was transfected with an IGFBP-rP1 expression vector. When injected intraperitoneally or subcutaneously into nude mice, the IGFBP-rP1-expressing EJ-1 and DLD-1 cell lines grew poorly, whereas the IGFBP-rP1 non-producers grew rapidly and produced large tumors. In monolayer culture the IGFBP-rP1 producers and non-producers grew similarly in each model, whereas in soft agar culture the former produced far less colonies than the latter. The IGFBP-rP1 producers had IGFBP-rP1 bound to the cell surface, and adhered more efficiently to fibronectin and laminin-5 than the respective non-producers. Expression of IGFBP-rP1 did not affect the efficiency of insulin signaling. These results demonstrate that IGFBP-rP1 strongly suppresses tumor growth by an insulin-independent or insulin-like growth factor-independent mechanism. Cell surface IGFBP-rP1 may reduce the anchorage-independent growth ability, leading to the marked loss of tumorigenicity.

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