Cell Culture Studies: A Perspective on Malignant Progression of Human Breast Cancer

Abstract

Primary breast cancers contain heterogeneous subpopulations which vary in the extent to which they are capable of aspects of metastatic spread. The conditions for cell isolation and culture, may select among differing populations. Using a system developed for culturing normal mammary epithelium, we have grown and characterized tumor-derived populations that appear to be partially transformed. The cells are invasive and show other characteristics distinguishing them from normal cells, but remain diploid. Because similar populations are not found in metastatic effusions, we hypothesize that the diploid cells represent an early stage of malignant progression. Such populations, which also have been isolated from hypodermal chest wall recurrences, have been used in a clonogenic assay for chemotherapeutic drug sensitivity, and the initial clinical correlations are promising.

Cultures derived from metastic effusions are highly variable in growth properties and usually do not clone with high efficiency. All are aneuploid. Unlike experimental models where metastases appear to be monoclonal (1), karyotypic polyclonality has been detected at first passage (2,3). Upon subculture, some effusions cease proliferation while others undergo crisis and develop into cell lines. In one case where the cells at first passage were polyclonal, the line that emerged subsequently was monoclonal indicating the degree of selection that can occur during the development of cell lines. Further studies to isolate and culture various populations from human breast cancers are needed because the cultured subsets can illustrate different links in the chain of events connecting biochemical and molecular studies on cell lines to studies of human cancer in vivo.