Effect of bone proteins on human prostate cancer cell lines in vitro.
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.
Hullinger
T G
TG
Department of Pharmacology, School of Medicine, University of Michigan, Ann Arbor 48109-1078, USA. tghullin@umich.edu
McCauley
L K
LK
DeJoode
M L
ML
Somerman
M J
MJ
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D001859:Bone Neoplasms / Q000556:secondary; D001842:Bone and Bones / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014020:Tissue Extracts / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D014020:Tissue Extracts