The regulation of prostate cancer cell adhesion to human bone marrow endothelial cell monolayers by androgen dihydrotestosterone and cytokines

Carlton R. Cooper, Jasmine K. Bhatia, Heather J. Muenchen, Lisa McLean, Satoru Hayasaka, Jeremy Taylor, Paul J. Poncza, Kenneth J. Pienta

Research output: Contribution to journalArticlepeer-review

Abstract

A previous study from our laboratory suggested that prostate cancer metastasis to bone may be mediated, in part, by preferential adhesion to human bone marrow endothelial (HBME) cells. Tumor cell adhesion to endothelial cells may be modulated by the effect of cytokines on cell adhesion molecules (CAMs). Tumor necrosis factor-alpha (TNF-α) regulates VCAM expression on the endothelium and this effect is enhanced by dihydrotestosterone (DHT). Transforming growth factor-beta (TGF-β) stimulates the expression of α2β1integrin on PC-3 cells. The current study investigated the effects of the above cytokines and DHT (singularly and in various combinations) upon HBME and prostate cancer cell expression of VCAM, α2 integrin subunit, and β1 integrin subunit by flow cytometry. We also monitored the effects of the above treatments on PC-3 cell adhesion to HBME monolayers. The data demonstrate that none of the treatments significantly altered the expression of selected CAMs on HBME cell and neoplastic prostate cell lines. The treatment of HBME monolayers with various combinations of cytokines and DHT prior to performing adhesion assays with PC-3 demonstrates that treatments containing TGF-β reduced PC-3 cell adhesion to HBME monolayers by 32% or greater (P < 0.05). The reduction in PC-3 cell adhesion to TGF-β-treated HBME monolayers was dose dependent. Interestingly, LNCaP cells but not PC-3 cells treated with TGF-β had a reduced ability to adhere to untreated HBME monolayers. These results suggest that TGF-β may reduce tumor cell adhesion to bone marrow microvascular endothelium, in vivo. The biological significance of this observation is discussed.

Original languageEnglish (US)
Pages (from-to)25-33
Number of pages9
JournalClinical and Experimental Metastasis
Volume19
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Dihydrotestosterone (DHT)
  • Human bone marrow endothelial cells
  • Human prostate cancer cells
  • Transforming growth factor-β
  • Tumor cell adhesion

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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