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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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. (Cancer Sci 2007; 98: 1055–1063)

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