Preferential adhesion of prostate cancer cells to a human bone marrow endothelial cell line

Jeffrey E. Lehr, Kenneth Pienta

Research output: Contribution to journalArticle

Abstract

Background: In virtually all patients with advanced prostate cancer, the disease metastasizes to bone and causes osteoblastic growth. However, the mechanisms that contribute to bone metastasis are poorly understood. It has been hypothesized that the bone provides a favorable growth environment for prostate cancer cells, which nonselectively seed the bone marrow from the bloodstream. Alternatively, prostate cancer cells may preferentially bind to bone marrow endothelial cells. We developed an in vitro model of bone endothelium and tested the hypothesis that prostate cancer cells adhere preferentially to bone marrow endothelial cells. Methods: We isolated and characterized a human bone marrow endothelial (HBME-1) cell line. Cells were transfected with the simian virus 40 large T antigen for immortalization. Cell surface receptors were characterized by immunohistochemistry and flow cytometry. The adhesion of cancer cells to HBME-1 and to endothelial cell lines from other organs was tested in an in vitro binding assay as were inhibitors of adhesion. Results: The immortalized HBME-1 cell line demonstrated many properties characteristic of endothelial cells, including positive staining for von Willibrand factor and rapid formation of tubule structures when exposed to extracellular matrices. In an in vitro assay, prostate cancer cells adhered preferentially to human bone marrow endothelium when compared with endothelium derived from other sources. Preferential adhesion was blocked, in part, by antibodies to galectin-3 and LFA-1. Implications: These data suggest that the propensity of prostate cancer cells to establish themselves in bone is due, at least in part, to their preferential adhesion to human bone marrow endothelial cells.

Original languageEnglish (US)
Pages (from-to)118-123
Number of pages6
JournalJournal of the National Cancer Institute
Volume90
Issue number2
Publication statusPublished - Jan 21 1998
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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