Search

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.

1,2-Dimethylhydrazine dihydrochloride (DMH) is one of the most reliable carcinogens for experimental colonic carcinogenesis. In order to evaluate the biological significances of target organ specificity of DMH-induced carcinogenesis, specific pathogen free (SPF) BALB/c mice were injected subcutaneously with DMH for 30 weeks, and were studied pathologically for tumor development of various organs. The data showed that colon tumor developed only at 2% of these mice. However, it produced 100% incidence of malignant endotheliomas and angiosarcomas of blood vessels and these tumors selectively appeared in the liver. There were no overt foci of primary vascular tumors in the heart, lung, kidney, muscle as well as spleen. This tumor model may reveal that the organ specificity of the carcinogenic activity with DMH could be converted, possibly depending upon the bacterial flora in the intestines, and very suitable for the investigation of implications of intestinal bacteria on the colonic and vascular tumorigenesis.