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Effect of bone proteins on human prostate cancer cell lines in vitro
T G Hullinger1, L K McCauley, M L DeJoode
1Department of Pharmacology, School of Medicine, University of Michigan, Ann Arbor 48109-1078, USA. tghullin@umich.edu
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.