Tumor cell dissemination patterns and metastasis of murine mammary carcinoma

Quantitative studies on the distribution kinetics of isotope-labeled cells from spontaneous murine mammary tumors injected intravenously or arterially showed that cells were rapidly distributed to all organs examined and indicated that the distribution patterns of metastases from such tumors are not primarily determined by the dose of cells delivered to each organ. The preferential colonization of certain organs is therefore considered to depend as much on differential survival and growth of the disseminated tumor cells in unfamiliar metabolic microenvironments, as on vascular sieving effects in organ capillary networks. Further experiments involved transplantation of pieces of nonpulmonary tissue containing trapped mammary tumor cells into syngeneic mice, followed by observation of the animals for several months. From these studies it is concluded that the absence of tumor colonies in extrapulmonary sites after i.v. inoculation is due to their inability to thrive in the organs concerned and not to early death of the original host from heavy pulmonary tumor growth. These results provide further evidence strengthening the conclusion emerging from several independent lines of investigation (Potter et al., Invasion Metastasis, 3: 221-233, 1983; Tarin et al., Cancer Res., 41: 3604-3609, 1981; Tarin et al., Cancer Res., 44: 3584-3592, 1984; Horak et al., J. Natl. Cancer Inst., 76: 913-922, 1986; Nicolson et al., Int. J. Cancer, 38: 289-294, 1986; Naito et al., Invasion Metastasis, 7: 16-29, 1987) that the growth of disseminated tumor cells is inhibited or even abrogated by many of the organs in which the cells sequester after vascular dissemination.