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Stromal fibroblasts are required for PC-3 human prostate cancer cells to produce capillary-like formation of endothelial cells in a three-dimensional co-culture system.

The outcome of patients with prostate cancer is largely dependent on the ability of the primary tumor for local invasion, angiogenesis and metastasis. To better understand the cell-cell interactions that participate in prostate cancer neovascularization, we have developed a novel three-dimensional co-culture system. Capillary-like structures were induced in fibrin gel in which collagen gels containing fibroblasts and/or PC-3 human prostate adenocarcinoma cells were sandwiched together. In the presence of collagen-embedded fibroblasts, angiogenesis apparently occurred, while endothelial cells did not survive when only PC-3 cells were embedded in collagen. In contrast, when PC-3 cells were combined with fibroblasts in collagen gel an enhanced formation of capillary-like structure formation was noted, particularly using FGF-2-supplemented medium. In addition, we observed morphological evidence of PC-3 cells and fibroblast invasion into fibrin using this system. Therefore, we conclude that fibroblasts apparently play an important role in angiogenesis and tumor invasion. Furthermore, this novel three-dimensional co-culture is apparently a promising model for studying de novo angiogenesis and tumor invasion in vitro.