Blocking an Interleukin-8 Receptor Reduces Breast Tumor Size and Prevents Metastasis

Blocking the receptor for interleukin-8 (IL-8) on cancer stem cells (CSCs) leads to significant reduction in the size of breast tumors and prevents metastasis. Cancer stem cells are considered resistant to current chemotherapies and radiation treatment, which may explain why cancer frequently reappears after initially successful treatment.

Investigators at the University of Michigan (Ann Arbor, USA) worked with both in vitro assays and mouse models to examine the effects of blocking the IL-8 receptor CXCR1 on the population of breast tumor CSCs. Activity of CXCR1 was blocked with either specific monoclonal antibodies or by the drug repertaxin, an anti-inflammatory agent originally developed to prevent organ transplant rejection.
Results published in the January 4, 2010, online edition of Journal of Clinical Investigation revealed that blocking CXCR1 selectively depleted the CSC population in two human breast cancer-cell lines in vitro. Furthermore, this reduction in cell number was followed by the induction of massive apoptosis in the bulk tumor population. In mice carrying human breast cancer xenografts, repertaxin was able to specifically target the CSC population, retarding tumor growth and reducing metastasis.

"These studies suggest that important links between inflammation, tissue damage, and breast cancer may be mediated by cancer stem cells. Furthermore, anti-inflammatory drugs such as repertaxin may provide a means of blocking these interactions, thereby targeting breast cancer stem cells," said senior author Dr. Max S. Wicha, professor of oncology at the University of Michigan. "Developing treatments to effectively target the cancer stem cell population is essential for improving outcomes. This work suggests a new strategy to target cancer stem cells that can be readily translated into the clinic."

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