Background:
Despite the high incidence and serious consequences of skeletal metastasis in prostate cancer patients, the mechanisms involved in establishing secondary lesions in bone are not well-understood. in this study, the role of the mineralized bone matrix in the process of skeletal metastasis was evaluated.
Methods:
Attachment, migration, and proliferation responses of human prostate cancer cells to a crude bone protein extract (cbe) were studied. lncap and du145 cells were utilized in 24-hr attachment assays. boyden chamber chemotactic assays and cell proliferation assays utilized du145 cells.
Results:
Cbe and fibronectin (fn) promoted attachment of du145 cells, whereas only fn facilitated attachment of lncap cells. cbe-mediated adhesion of du145 cells was reduced by 94% with cycloheximide, by 98% with rgd peptides, and by 94% with an antibody to alphavbeta3. although du145 cells migrated toward fn, cbe did not promote migration of du145 cells. du145 cells grown in the presence of cbe-containing media demonstrated a significant reduction in cell number by day 4. the antiproliferative effect of cbe was not due to cell toxicity.
Conclusions:
In conclusion, results from this study indicate that mineralized bone proteins promote the attachment of du145 cells in vitro and suggest that bone proteins may play a key role in vivo during the development of metastatic prostate lesions in bone.