Abstract
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 Mn and Mg ions and was RGD-independent. Antibodies directed against β1 or α2 integrin subunits inhibited adhesion to collagen by 90% and 53%, respectively, suggesting involvement of the α2β1 receptor. Anti-α1 or anti-α3 antibodies had no effect on adhesion. Flow cytometry and immunoprecipitation of [S]methionine-labeled cells demonstrated that α2β1 was the major collagen receptor expressed by PC-3 cells. The pretreatment of PC-3 cells with transforming growth factor-β1 (TGF-β1), a major bone-derived growth factor, caused a rapid (2 h) 2-fold increase in the de novo synthesis of α2 and β1 integrin subunits, and also increased by 2- to 3-fold the adhesion and spreading of PC-3 cells on collagen. We conclude that α2β1 is the major collagen receptor employed by PC-3 cells, and that α2β1 upregulation by TGF-β 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-β in bone may promote their ability to adhere to bone-derived collagen, which may thereby facilitate the localization of metastatic cells in the skeleton.
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Kostenuik, P.J., Singh, G. & Orr, F. Transforming growth factor β upregulates the integrin-mediated adhesion of human prostatic carcinoma cells to type I collagen. Clin Exp Metastasis 15, 41–52 (1997). https://doi.org/10.1023/A:1018484323210
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DOI: https://doi.org/10.1023/A:1018484323210