The potential for estrogen disrupting chemicals to contribute to migration, invasion and metastasis of human breast cancer cells

Abstract

Estrogen disrupting chemicals are environmental compounds which mimic, antagonize or interfere in the action of physiological estrogens. They occur naturally (plant phytoestrogens) but the majority are man-made compounds, which, through their use in agricultural, industrial and consumer products, have become widely present in human tissues including breast tissue. Since exposure to estrogen is a risk factor for breast cancer, estrogen disrupting chemicals may also contribute to breast cancer development. This review discusses evidence implicating estrogen disrupting chemicals in increasing migratory and invasive activity of breast epithelial cells, in epithelial-tomesenchymal transition, and in growth of breast tumours at metastatic sites as well as the primary site. Mechanisms may be through the ability of such chemicals to bind to estrogen receptors, but unlike for proliferation, effects on cell migration and invasion are not limited to estrogen receptor-mediated mechanisms. Furthermore, whilst effects on proliferation can be measured within hours/days of adding an estrogen disrupting chemical to estrogen-responsive breast cancer cells, effects on cell migration occur after longer times (weeks). Most studies have focused on individual chemicals, but there is now a need to consider the environmentally relevant effects of long-term, lowdose exposure to complex mixtures of estrogen disrupting chemicals on mechanisms of metastasis.