Richard George Pestell
Pennsylvania Cancer and Regenerative Medicine Research Center, USA
Title: CCR5 governs stem cell characteristics, therapy resistance and metastasis of breast cancer
Biography
Biography: Richard George Pestell
Abstract
Recent studies have demonstrated a propensity of tumor initiating cells with stem cell-like features to contribute to metastasis and therapy resistance. The mechanisms by which cancer stem cells survive chemotherapy- and radiotherapy is not well understood. We herein describe the novel finding that the immune chemokine receptor CCR5 is selectively expressed on transformed breast epithelial cells, promoting breast cancer stem cell expansion and DNA damage repair. Reintroduction of CCR5 into CCR5-negative cells promoted breast tumor stem cell expansion, metastases, and the induction of DNA repair gene expression. CCR5 was shown to enhance the repair of Double Stranded DNA Breaks (DSBS) by inducing HDR and SSA-based DNA repair. Single cell sequencing documented activation of gene expression pathways mediating ribosomal biogenesis and cell survival in CCR5+ cells. In a broad array of BRCA1mutant breast cancer cell lines DNA damaging chemotherapeutic agent-mediated cell killing was dramatically enhanced by CCR5 antagonists. Because CCR5 is expressed only on the breast cancer epithelial cells the current findings illustrate CCR5 inhibitors enhance the tumor specific activities of DDR-based treatments.