Interleukin-8 secreted by endothelial cells induces chemotaxis of melanoma cells through the chemokine receptor CXCR1

SPECIFIC AIMMigration of tumor cells is an important step in the process of tumor metastasis. Tumor cells must traverse the endothelial lining of the lymphatic and vascular systems in order to metastasize to distant organs. We test the hypothesis that endothelial cells secrete chemoattractants that induce chemotaxis of tumor cells across the endothelium.PRINCIPAL FINDINGSConditioned endothelial medium was tested for its chemoattractant activity on metastatic melanoma cells in under-agarose migration and transwell migration assays. Interleukin (IL) -8 was identified as the major endothelium-secreted chemokine for metastatic melanoma cells. Antibody neutralization studies indicated that IL-8 elicits chemotactic response through the chemokine receptor CXCR1 (IL-8RA) on melanoma cells. Migration of melanoma cells across the endothelium was inhibited by antibodies against IL-8 or CXCR1, suggesting a role for the endothelium-secreted IL-8 at the transendothelial migration stage of cancer metastasis.1. Endotheli...