Transforming growth factor beta upregulates the integrin-mediated adhesion of human prostatic carcinoma cells to type I collagen.
Prostate cancer frequently metastasizes to bone, and we propose that this process may be facilitated by the adhesion of metastatic cells to bone-derived type I collagen. We examined collagen receptor function and regulation in osteotropic PC-3 human prostatic carcinoma cells. PC-3 cell adhesion to immobilized human type I collagen was promoted by Mn2+ and Mg2+ ions and was RGD-independent. Antibodies directed against beta1 or alpha2 integrin subunits inhibited adhesion to collagen by 90% and 53%, respectively, suggesting involvement of the alpha2 beta1 receptor. Anti-alpha1 or anti-alpha3 antibodies had no effect on adhesion. Flow cytometry and immunoprecipitation of [35S]methionine-labeled cells demonstrated that alpha2 beta1 was the major collagen receptor expressed by PC-3 cells. The pretreatment of PC-3 cells with transforming growth factor-beta1 (TGF-beta1), a major bone-derived growth factor, caused a rapid (2 h) 2-fold increase in the de novo synthesis of alpha2 and beta1 integrin subunits, and also increased by 2- to 3-fold the adhesion and spreading of PC-3 cells on collagen. We conclude that alpha2 beta1 is the major collagen receptor employed by PC-3 cells, and that alpha2 beta1 upregulation by TGF-beta is associated with an increased adhesion and spreading on collagen. The data suggest that exposure of metastatic PC-3 cells to the high levels of TGF-beta in bone may promote their ability to adhere to bone-derived collagen, which may thereby facilitate the localization of metastatic cells in the skeleton.
Kostenuik
P J
PJ
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Singh
G
G
Orr
F W
FW
D000230:Adenocarcinoma / Q000473:pathology* / Q000556:secondary; D001859:Bone Neoplasms / Q000556:secondary*; D001842:Bone and Bones / Q000737:chemistry; D002413:Cations, Divalent / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D048429:Cell Size; D003094:Collagen / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010446:Peptide Fragments / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000473:pathology*; D038981:Receptors, Collagen; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects*
D002413:Cations, Divalent; D016023:Integrins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D038981:Receptors, Collagen; D016212:Transforming Growth Factor beta; D003094:Collagen