Robin Bachelder
Duke University Medical Center
Durham
Title: Chemo-residual Triple-Negative Breast Tumor cells Exhibit Increased Metastatic Potential
Biography
Biography: Robin Bachelder
Abstract
Although many tumors are initially responsive to chemotherapy, residual tumor cells frequently persist, and are thought to be responsible for future tumor growth at local and distant sites. Recent studies indicate that chemotherapy can alter the tumor microenvironment in a manner that enables increased tumor metastasis. However, to date, an ability of chemotherapy to promote tumor metastasis by directly influencing tumor cell signaling has not been demonstrated. In the current study, we show that short-term exposure of triple-negative breast tumor cells to chemotherapy in vitro results in: 1) die-off of the majority of tumor cells, and 2) survival of chemo-residual tumor cells with increased invasive and metastatic potential. Notably, tumor cells derived from our short-term chemotherapy model do not exhibit increased cancer stem cell behaviors relative to untreated tumor cells. We demonstrate that tumor cells surviving short-term chemotherapy express a pro-form of an adhesion molecule (Pro-N-cadherin) on their cell surface, which drives their invasive behavior. Collectively, our results indicate that short-term chemotherapy treatment models can identify novel signaling molecules in chemo-residual tumor cells that confer a metastatic phenotype. Importantly, our findings also suggest that chemotherapy enriches for a subset of triple-negative tumor cells with enhanced metastatic potential.