Depleting breast cancer-initiating cells by targeting the protein CXCR1

Recent data suggest that many types of cancer, including breast cancer, are initiated and maintained by a rare population of cells within the tumor known as cancer stem cells. These cells are thought also to contribute to tumor spread (metastasis) and recurrence after treatment, meaning that many researchers are seeking to develop approaches to target them. A team of researchers, at the University of Michigan Comprehensive Cancer Center, Ann Arbor, and U891/Inserm/Institut Paoli-Calmettes, France, has now identified a strategy to target human breast cancer stem cells that decreased tumor growth and metastasis in mice xenotransplanted with human breast cancer cells. The team, led by Max Wicha and Christophe Ginestier, found that inhibiting the cell surface protein CXCR1, with either an antibody or a small molecule known as repertaxin, selectively depleted the cancer stem cell population in two human breast cancer cell lines in vitro. Loss of the cancer stem cells was followed by extensive death of many of the remaining tumor cells. Importantly, treatment with repertaxin had similar effects in mice xenotransplanted with human breast cancer cells: cancer stem cells were selectively depleted leading to a reduction in tumor growth and metastasis. The authors therefore suggest that strategies that target CXCR1, the soluble protein that binds to it, and the signaling pathways downstream of it might provide a good approach to deplete breast cancer stem cells and prove beneficial to women with breast cancer.

Source: Journal of Clinical Investigation