Sequential process of blood-borne lung metastases of spontaneous mammary carcinoma in C3H mice.

We examined the correlation between growth characteristics and the incidence of lung metastases of spontaneous mammary tumors in C3H mice. The growth pattern of the mammary tumors was composed of initial rapid growth, declining growth, and further exponential growth (re-growth). The "re-growth" was closely associated with loss of differentiation and progressive increase of the incidence of lung metastases. In addition, we observed the sequential process of blood-borne lung metastases. The findings involved (i) "passive" intravasation: carcinoma nests encased in newly formed endothelial cells are released into sinusoidal vessels within primary tumors; (ii) "mechanical" arrest and proliferation of multicellular tumor emboli in pulmonary arterioles; (iii) "active" extravasation: carcinoma cells rushed out to the lung parenchyma through the arteriolar walls ruptured by initial minimal penetration of carcinoma cells and intravascular pressure. The results indicate a stable progression in the natural history of C3H mouse mammary carcinomas characterized by growth characteristics, the incidence of lung metastases, and histological change generating a poorly differentiated clone which can successfully complete a sequential process of blood-borne lung metastasis.