Validation of an in vitro model of erbB2(+) cancer cell redirection.

Abstract

Overexpression of the oncoprotein erbB2/HER2 is present in 20-30% of breast cancer patients and inversely correlates with patient survival. Reports have demonstrated the deterministic power of the mammary microenvironment where the normal mammary microenvironment redirects cells of non-mammary origin or tumor-derived cells to adopt a mammary phenotype in an in vivo model. This phenomenon is termed tumor cell redirection. Tumor-derived cells that overexpress the erbB2 oncoprotein lose their tumor-forming capacity in this model. In this model, phosphorylation of erbB2 is attenuated thus reducing the tumor cell's tumor-forming potential. In this report, we describe our results using an in vitro model based on the in vivo model mentioned previously. Tumor-derived cells are mixed in predetermined ratios with normal mammary epithelial cells prior to seeding in vitro. In this in vitro model, the tumor-derived cells are redirected as determined by attenuated phosphorylation of the receptor and reduced sphere and colony formation. These results match those observed in the in vivo model. This in vitro model will allow expanded experimental options in the future to determine additional aspects of tumor cell redirection that can be translated to other types of cancer.