PRIMARY PROSTATIC EPITHELIAL-CELL BINDING TO HUMAN BONE-MARROW STROMAAND THE ROLE OF ALPHA-2-BETA-1 INTEGRIN

Prostate cancer selectively metastasises to the bone, To investigate t he importance of prostate epithelial cell adhesion to bone marrow cell s in this profess we examined the binding of human primary prostatic e pithelial cells (PEG) to human bone marrow stromal cultures (BMS), We found that PEC derived from both malignant and benign tissue showed gr eater adhesion to BMS than to benign prostatic fibroblasts (median dif ference was 340% and 200% respectively), skin fibroblasts or plastic t issue culture plates, Adhesion to EMS grown from the bone marrow of pa tients with prostatic skeletal metastases was no different from those grown from normal bone marrow, The role of integrin molecules in these cell interactions was determined, Collagen type I and fibronectin wer e found to increase PEC adhesion whereas vitronectin and laminin did n ot, Inhibition studies demonstrated that although there was heterogene ity between samples, antibodies against the integrins alpha 2 and beta 1 consistently inhibited PEC binding to BMS, This result was more mar ked for PEC derived from malignant tissue, However studies investigati ng the effects of disintegrins and anti-alpha 3 and anti-alpha 5 integ rins indicated that for a percentage of patients these integrins and R GD (arginine, glycine, aspartamine)-dependent binding pathways were al so involved. In summary, the results indicate that EMS are adherent to primary PEC derived from both malignant and benign tissue, The integr in alpha 2 beta 1 is a major contributor to this interaction.