Interaction of prostate epithelial cells from benign and malignant tumor tissue with bone-marrow stroma.
BACKGROUND
Metastases of prostate cancer form selectively within the skeleton. To understand this metastatic spread, we studied the ability of prostate epithelial cells to grow and proliferate within the bone marrow, using primary coculture.


METHODS
Prostate epithelia and fibroblasts were prepared from men with benign prostatic hyperplasia (n = 13) and cancer of the prostate (n = 10). Confluent cultures of bone-marrow stroma or fibroblast controls were prepared in 96-well plates, and identical plates were treated with detergent to expose the extracellular matrix of the cells. Epithelial cells were seeded onto either cells or matrix, and their growth characteristics were determined by counting increases in colony size and number over time. Further experiments evaluated the effects on epithelial growth when cells were exposed to media conditioned by these stroma, using an MTT assay.


RESULTS
Results showed that for epithelial cells derived from malignant (or benign) tissue, the median value of the total area of colonies formed on bone-marrow stroma was 2.1 (benign, 2.6) mm2, in contrast to 0.3 (benign, 0.4) mm2 or 0.25 (benign, 0) mm2 when these cells were cocultured with fibroblasts from benign or malignant prostates, respectively. Statistics indicated that growth was significantly greater on bone-marrow stroma than on control stroma (P < 0.005). However, no significant stimulation of epithelial cell growth was seen when these epithelial cells were cultured on extracellular matrix from bone-marrow stroma or when exposed to bone-marrow stroma-conditioned media in comparison to fibroblast controls. No statistical differences were found between the formation of colonies from malignant tissue in comparison to benign.


CONCLUSIONS
This system allows the investigation of bone-marrow stroma colonization by primary prostate epithelial cells, and could be developed for the study of metastasis.
Lang
S H
SH
Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Manchester, UK. shl2@york.ac.uk
Clarke
N W
NW
George
N J
NJ
Allen
T D
TD
Testa
N G
NG
D001854:Bone Marrow Cells / Q000166:cytology*; D002450:Cell Communication; D002455:Cell Division; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D004847:Epithelial Cells / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D009362:Neoplasm Metastasis; D011467:Prostate / Q000473:pathology* / Q000648:ultrastructure; D011470:Prostatic Hyperplasia / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000648:ultrastructure; D017154:Stromal Cells / Q000166:cytology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned