Bi-directional interactions of prostate cancer cells and bone marrow endothelial cells in three-dimensional culture

BACKGROUND. Prostate cancer preferentially metastasizes to bone, yet little is known about the cellular and molecular factors that support this growth. Endothelial cells are likely the initial contact for circulating prostate cells entering the bone microenvironment. METHODS. Using co-culture and conditioned media experiments, we studied cellular and molecular interactions of prostate cancer cells of varying aggressiveness (PC-3 and LNCaP) with bone marrow endothelial (HBME-1) cells in collagen gels. RESULTS. In co-culture, HBME-1 cells stimulated proliferation (similar to 90% increase) and migration of the more aggressive PC-3 cell line, while having little effect on LNCaP cell proliferation or migration. Concomitantly, HBME-l cell growth was inhibited by both PC-3 and LNCaP cells and their conditioned media. Additionally, HBME-1 cells underwent significant morphological changes in co-culture, forming large, branching, cord-like structures, which mimic angiogenesis. Prostate cancer cell conditioned media induced a similar effect on HBME-1 cells. In comparison, conditioned media from PC-3 cells also inhibited growth of non-bone marrow-derived endothelial cells, but did not affect their morphology. CONCLUSIONS. Significant bi-directional interactions, including secreted factors and direct cellular interactions, exist between bone marrow endothelial cells and highly metastatic prostate cancer cells, and may underlie the propensity for prostate cancer to metastasize to the bone. (c) 2005 Wiley-Liss, Inc.