Influence of microenvironment and vascular anatomy on "metastatic" colonization potential of mammary tumors

Abstract

This communication reports experiments demonstrating that some sites in which tumor cells lodge reproducibly fail to support secondary colony formation by a particular tumor, even though cells from the same tumor are already proven to have high colonization potential in other organs. The effect is not an expression of nonspecific hostility to tumor growth, since cells from certain other tumors readily colonize the same site. Cell suspensions obtained by disaggregation of a series of naturally occurring murine mammary tumors were each inoculated by four different routes into separate batches of syngeneic animals, and the resulting degree and distribution of colonization were studied 90 days later at autopsy. Standard doses of 1 million viable tumor cells were injected either i.p. or s.c. into the tail vein or the hepatic portal vein. It was found that some tumors could reproducibly colonize by all routes, whereas others could colonize only by a few, and the combination of sites colonized varied from tumor to tumor; still others were unable to grow in any site. Cells from nonneoplastic lactating mammary glands did not establish any colonies. We have demonstrated previously that individual naturally occurring mammary tumors differ in their pulmonary colonization potentials after i.v. inoculation and that the potential of a given tumor is an intrinsic property of its constituent cells. The current findings are evidence that the microenvironment of an organ can inhibit or permit expression of this intrinsic potential and that the degree and sites of colonization are thus the results of interaction between tumor and organ-specific factors. It was also found that circulatory anatomy partially influenced the distribution of colonies and that colonization of distant organs after blood-borne dissemination is distinct from general tumor transplantability.