Experimental metastasis of mouse embryonal carcinoma cell lines to specific locations.

Embryonal carcinoma cell lines produced tumors in highly specific and unusual sites when injected into mice. The pattern that developed when cells were injected into the left ventricle of the heart involved target organs related either to specific nerve patterns or neuronal outgrowth factors, or to pathways of primordial germ cell migration. Major sites included the ovary, testis, adrenal, iris, whiskers, and male submaxillary gland. Neither local growth responses, determined by direct injection of tumor cells into different organ parenchyma, nor initial attachments, observed upon injection of radiolabeled cells, appeared to sufficiently account for the specificity of tumor metastases occurring after arterial injection. However, tissue from uninjected target sites, but not other tissues, stimulated the in vitro migration of embryonal carcinoma cells. Conditioned medium from only target tissues had a similar effect. These results suggest that the specificity of this tumor pattern may depend on migration responses that are significant in the localization of embryonic germ and neural cells. The specific metastatic pattern observed following i.p. injection of embryonal carcinoma cells, involving only the ovary, appeared to require an additional component of high adhesivity to the target organ.