Hemodynamic considerations in organ and tissue patterning of B16 melanoma systemic metastasis and colonization

Abstract

Several populations of the mouse B16 melanoma that are highly metastatic from subcutaneous transplants but differ in growth characteristics were compared with regard to systemic site patterning of visible metastasis, as well as colonization effected by intracardiac injection of tumor cells. In all cases, metastasis proceeded in two stages, initially to the lungs and secondarily from lung metastases to systemic sites. The relative ranking of systemic site involvement by secondary-stage metastasis was basically similar for all tumor cell populations; the overall hierarchy was: kidneys greater than brain greater than adrenals and ovaries greater than pancreas greater than mesentery. Colonization patterns resulting from intracardiac injection were also generally comparable but differed from metastasis patterning in that the kidneys and brain were poorly colonized while the bones were frequent sites of colonization. Enumeration of fluoresceinated tumor cells or microbeads trapped in various sites following intracardiac injection revealed a ranking of initial involvement that differed markedly from colony formation. These results indicate that the hemodynamics of blood flow is not a critical determinant of colonization patterning. Based on the colonizing behavior of microbead-bound tumor cells, the frequent metastatic involvement of the kidneys and brain appears to result from selective trapping of large multicell tumor emboli within arteries in those organs. The occurrence of metastasis in other systemic sites is, like colonization, not readily explained by hemodynamics.