Bowes melanoma cells secrete heregulin, which can promote aggregation and counteract invasion of human mammary cancer cells

Invasiveness, the ability of cancer cells to migrate beyond the normal tissue boundaries, often leads to metastasis and thereby usually turns cancer into a fatal disease. At the molecular level, the E‐cadherin/catenin complex is an example of a powerful invasion suppressor in epithelial cells. Since the absence of melanocytes has been associated with disturbances in epithelial organization, we decided to investigate the influence of molecules secreted by melanocytes on the function of the E‐cadherin/catenin complex. We used the Bowes melanoma cell line as a source of such molecules. The conditioned medium of Bowes melanoma stimulated aggregation of human MCF‐7/6 mammary adenocarcinoma cells at short (30 min) and long (24–72 hr) notice. This effect could be inhibited by MB2, an antibody against human E‐cadherin. Conditioned medium of Bowes melanoma also inhibited invasion of MCF‐7/6 cells into precultured chick heart fragments. Candidate molecules such as insulin, insulin‐like growth factor I, follistatin and interleukins were ruled out to be responsible for the effects, but heregulin mimicked some of the effects of the conditioned medium. Our data indicate that heregulin stimulates aggregation and inhibits invasion of MCF‐7/6 cells via activation of the E‐cadherin/catenin complex. © 2005 Wiley‐Liss, Inc.