Growth Factor Synthesis and Human Breast Cancer Progression

Abstract

Data obtained using long-established human breast cancer cell lines have suggested that autocrine growth factors secreted by the cells are important for their growth in vitro. Such data alone cannot definitively establish a role for autocrine growth factors in human breast cancer cell proliferation in vivo, but they create a paradigm that can be tested by analysis of data obtained with primary breast cancer cells and tissues. This review is aimed at examining experimental data obtained using fresh human breast cancer cells and tissues to determine whether the results obtained are consistent with predictions made by autocrine models of human breast cancer cell proliferation. Conceptually, for autocrine loops to be of primary importance in human breast cancer cell proliferation, breast cancer cells in vivo must 1) synthesize biologically active growth factors that are available to growth factor receptors, 2) synthesize the cognate growth factor receptors, 3) require the specific factors for proliferation, and 4) express the autocrine loop as a pathologic, rather than a physiologic, process. Since the proportion of tumors that express growth factors of a given family is consistently higher than the proportion of tumors that express the cognate receptors, it is likely that growth factor synthesis has an important, nonautocrine role in breast cancer progression as well. Data obtained with primary human breast cancer specimens indicate that growth factors synthesized by breast cancer cells have an important role in tumor development and progression but that these factors act in a true autocrine fashion only in a subset of tumors.