RELAXIN AND BREAST-CANCER

Relaxin is a peptide hormone of luteal origin with a broad range of bi ological activities on tissues and organs of the female reproductive s ystem as well as on other targets not directly related to the reproduc tive function. The mammary gland is one of the major targets for relax in, which has been shown to promote growth and differentiation of mamm ary parenchyma and stroma. Based on the recognition of the mammotrophi c action of relaxin, further research could show that this peptide als o influences the behaviour of breast cancer cells in vitro. In fact, w hen relaxin was added to the culture medium of MCF-7 breast adenocarci noma cells for short exposure times it had a biphasic effect on their growth, stimulating cell proliferation at low, nanomolar concentration s and inhibiting it at high, micromolar concentrations. In the longer times, relaxin had a marked growth-inhibitory effect on MCF-7 cells at any concentration assayed, and concurrently promoted cell differentia tion and expression of adhesion molecules which are known to hinder th e spreading ability of cancer cells. The positive effect of relaxin on MCF-7 cell differentiation was even enhanced when these cells were co cultured with myoepithelial cells, thus recreating a microenvironment reminiscent of the tissue architecture of the mammary ducts in vivo. C oncerning the mechanisms of action of relaxin on MCF-7 cells, it seems that the growth-inhibiting and differentiation-promoting effects of t he peptide are mediated through the activation of the synthetic pathwa y of nitric oxide.