Expression of angiogenesis factors in monolayer culture, multicellular spheroid and in vivo transplanted tumor by human ovarian cancer cell lines.

We examined the expression of four angiogenesis factors (vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), platelet-derived endothelial cell growth factor (PD-ECGF) and basic fibroblast growth factor (bFGF)) in five human ovarian cancer cell lines by Northern blot analysis and immunohistochemical staining. The cancer cells were grown as a subconfluent monolayer culture, a multicellular aggregate (spheroid) in a three-dimensional culture, and a nude mouse-transplanted subcutaneous tumor in order to simulate the cellular conditions of ovarian cancers in peritonitis carcinomatosa, i.e. floating single tumor cells, multicellular aggregates and peritoneally implanted tumors. In each cell line, the expression of VEGF was detected in a monolayer culture and obviously enhanced in a three-dimensional culture. IL-8 was expressed in two of five cultured cell lines, but neither PD-ECGF nor bFGF was detected. Each cell line-derived transplanted tumor expressed immunohistochemical products of the four angiogenesis factors examined. These observations were confirmed by surgical specimens and suggested that ovarian cancer cells expressed different kinds and/or doses of angiogenesis factors depending on the form of the changed tumor cells during peritoneal implant formation.