Interactions of human prostatic epithelial cells with bone marrow endothelium: binding and invasion

Prostate cancer shows a propensity to form secondary tumours within the bon e marrow. Such tumours are the major cause of mortality in this disease. We have developed an in vitro system to study the binding of prostate epithel ial cells to bone marrow endothelium (BME) and stroma (BMS). The metastatic prostate cancer cell line, PC3 (derived from a bone metastasis), was seede d onto confluent layers of BME and its binding characteristics compared to human umbilical vein endothelial cells (HUVEC), lung endothelium (Hs888Lu) and EMS. The PC3 cell line showed significantly increased binding to BME (P < 0.05) compared to endothelium derived from HUVEC and lung or EMS with ma ximal binding occurring at 1 h. Following pre-incubation with a <beta>1 int egrin antibody PC3 binding to BME was inhibited by 64% (P < 0.001). Antibod ies directed against the integrins <beta>4, alpha2, alpha4,alpha5 and the c ellular adhesion molecules P-selectin, CD31, VCAM-1 and sialy Lewis X showe d no effect on blocking PC3 binding. Primary prostatic epithelial cells fro m both malignant (n = 11) and non-malignant tissue (n = 11) also demonstrat ed equivalent levels of increased adhesion to BME and EMS compared to HUVEC , peaking at 24 h. Further studies examined the invasive ability of prostat e epithelial cells in response to bone marrow endothelium using Matrigel in vasion chamber assays. In contrast to the previous results, malignant cells showed an increase (1000 fold) in invasive ability, whilst non-malignant p rostate epithelia did not respond. We have shown that both malignant and no n-malignant prostate epithelial cells can bind at equivalent levels and pre ferentially to primary human bone marrow endothelium in comparison to contr ols. However, only malignant prostate epithelia show increased invasive abi lity in response to BME. (C) 2001 Cancer Research Campaign.