Antiangiogenic substance(s) in a tumor cell line with low metastatic potential originating from the BALB/c mouse liver.

Two cell lines were established from liver cells (BALB/c mouse) exposed to benzo(a)pyrene: one was highly metastatic (G-5) and the other poorly metastatic (G-1) to the lung when subcutaneously implanted. However, there was no difference in lung colonization between G-1 and G-5 cells when they were intravenously injected. When G-1 cells were subcutaneously inoculated on one side of the back of mice followed by a challenge on the other side with G-5 cells 10 days later, the growth of the latter tumor was inhibited and the number of metastatic nodules in the lung was reduced. The functional vascular volume of G-1 tumor was less than the G-5 one. In mice bearing G-1 tumors, the neovascularization of intradermally inoculated G-5 cells was reduced. The conditioned medium from G-1 culture contained an inhibitory activity on the growth of endothelial cells from calf pulmonary artery. The inhibitory substance(s) was heat-stable, trichloroacetic acid-soluble, nondialyzable and resistant to various proteinases. The present results imply that G-1 cells produce an antiangiogenic substance(s), probably a polysaccharide(s), which inhibits the angiogenesis required for growth and metastasis of the G-5 tumor.