Strong suppression of tumor growth by insulin-like growth factor-binding protein-related protein 1/tumor-derived cell adhesion factor/mac25.
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.
Sato
Yuichiro
Y
Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, 641-12 Maioka-cho, Totsuka-ku, Yokohama 244-0813, Japan.
Chen
Zhaoxin
Z
Miyazaki
Kaoru
K
D000230:Adenocarcinoma / Q000473:pathology; D017209:Apoptosis; D001943:Breast Neoplasms / Q000473:pathology; D002448:Cell Adhesion; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics / Q000502:physiology*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000502:physiology*; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
C032231:IGFBP1 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; C102529:insulin-like growth factor binding protein-related protein 1