Induction of phenotypic changes in HER2-postive breast cancer cells in vivo and in vitro

Author:

Frank-Kamenetskii, Anastasia

Mook, Julia

Reeves, Meredith

Boulanger, Corinne A

Meyer,Thomas

Ragle, Lauren

Jordan, H Caroline

Smith, Gilbert H

Booth, Brian W
Author Address

Department of Bioengineering, Clemson University, Clemson, SC, USA., Department of Biological Sciences, Clemson University, Clemson, SC, USA., Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., CCR Collaborative Bioinformatics Resource, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., These authors contributed equally to this work.,

Abstract:

The influence of breast cancer cells on normal cells of the microenvironment, such as fibroblasts and macrophages, has been heavily studied but the influence of normal epithelial cells on breast cancer cells has not. Here using in vivo and in vitro models we demonstrate the impact epithelial cells and the mammary microenvironment can exert on breast cancer cells. Under specific conditions, signals that originate in epithelial cells can induce phenotypic and genotypic changes in cancer cells. We have termed this phenomenon "cancer cell redirection." Once breast cancer cells are redirected, either in vivo or in vitro, they lose their tumor forming capacity and undergo a genetic expression profile shift away from one that supports a cancer profile towards one that supports a non-tumorigenic epithelial profile. These findings indicate that epithelial cells and the normal microenvironment influence breast cancer cells and that under certain circumstances restrict proliferation of tumorigenic cells.

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