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

Clin Exp Metastasis. 1997 Jan;15(1):41-52. doi: 10.1023/a:1018484323210.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / pathology*
  • Adenocarcinoma / secondary
  • Bone Neoplasms / secondary*
  • Bone and Bones / chemistry
  • Cations, Divalent / metabolism
  • Cell Adhesion / drug effects
  • Cell Size
  • Collagen / metabolism*
  • Humans
  • Integrins / biosynthesis*
  • Integrins / genetics
  • Male
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Peptide Fragments / metabolism
  • Prostatic Neoplasms / pathology*
  • Receptors, Collagen
  • Transforming Growth Factor beta / pharmacology*
  • Tumor Cells, Cultured
  • Up-Regulation / drug effects*


  • Cations, Divalent
  • Integrins
  • Neoplasm Proteins
  • Peptide Fragments
  • Receptors, Collagen
  • Transforming Growth Factor beta
  • Collagen