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Transforming growth factor β upregulates the integrin-mediated adhesion of human prostatic carcinoma cells to type I collagen

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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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Authors and Affiliations

  1. Department of Pathology, McMaster University Hamilton, Ontario, Canada

    Paul J. Kostenuik

  2. Hamilton Regional Cancer Centre, 699 Concession St, Hamilton, Ontario, Canada

    Gurmit Singh

  3. Department of Pathology, University of Manitoba, 820 Sherbrook St, Winnipeg, Manitoba, Canada

    F.William Orr

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  1. Paul J. Kostenuik
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  2. Gurmit Singh
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  3. F.William Orr
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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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