Colonization characteristics of a murine mammary tumor cell line that metastasizes frequently to the heart

Abstract

Metastasis by mouse mammary tumor cells is usually confined to lung. This paper describes the metastatic behavior of an established mouse mammary tumor cell line, 4526, that in addition to lung and liver metastasis, shows a high rate of heart metastases. The tumor cells were inoculated into the fourth mammary fat pad of syngeneic mice and their pattern of distant colonization was analysed qualitatively as well as quantitatively. We found that the cell line produced 100, 70 and 40% metastases to the lung, liver and heart, respectively. While the lung metastases appeared primarily as nodular masses, the liver metastases occurred both as nodular and diffuse masses. In addition, we observed that the metastatic load of each of the different lung lobes of individual mice was proportional directly to its relative size, and there seemed to be an inverse relationship between the occurrence of lung and liver metastases in individual mice. As compared to lung and liver metastases, heart metastases were found to be localized internally, usually in the cavity and wall of the ventricle. Furthermore, hearts with metastases revealed destruction of cardiac tissue and blockage of the cavity space. Our results show that 4526 cells are phenotypically stable, since the metastatic behavior of several clonal derivatives of the cell line obtained from lung, liver and heart colonies were found to be identical to that of the parental cell line. Thus this cell line, because of its unparalleled metastatic characteristics, offers a model for investigations into the biology of mammary tumor cell metastasis, especially heart metastasis.