Novel Breast Cancer Therapy Targets Cancer Stem Cells
Blockade of interluekin-8 receptors killed stem cells in in vitro and mouse model experiments
THURSDAY, Jan. 14 (HealthDay News) -- Blockading interleukin 8 (IL-8) receptors to kill off cancer stem cells (CSCs) may be a novel approach to treating breast cancer, according to a study published Jan. 4 in the Journal of Clinical Investigation.
Christophe Ginestier, Ph.D., of the University of Michigan Comprehensive Cancer Center in Ann Arbor, and colleagues investigated the effects of the blockade of the IL-8 receptor CXCR1 on CSCs using in vitro breast cancer cell lines HCC1954, MDA-MB-453 and SUM159, and breast cancer cell xenografts in NOD/SCID mice. The researchers treated the cells with the small-molecule CXCR1 inhibitor repertaxin and alternatively a CXCR1-specific blocking antibody. Effects on the CSCs were observed by the cellular expression of aldehyde dehydrogenase as assessed by an ALDEFLUOR assay.
After three days of repertaxin treatment, the researchers reported a five-fold reduction of CSCs in the SUM159 cell line, with a similar effect seen after treatment with an anti-CXCR1 blocking antibody. After five days of repertaxin treatment, the viability of the entire cell population was severely impaired, leaving only 3 percent of cells viable. Repertaxin had a similar effect in the HCC1954 breast cancer cell line, but there was no effect in the MDA-MB-453 cells or for another IL-8 receptor, CXCR2. In the xenografts in the NOD/SCID mice, repertaxin retarded tumor growth and reduced breast cancer metastasis.
"Our data therefore suggest that CXCR1 blockade may provide a novel means of targeting and eliminating breast CSCs," the authors write.
One study author reported having financial holdings in and being a scientific adviser for OncoMed Pharmaceuticals. In addition, the University of Michigan has filed for patent protection for the technology used in the study.