Host CXCR2-dependent regulation of melanoma growth, angiogenesis, and experimental lung metastasis.

Abstract

Crucial steps in tumor growth and metastasis are proliferation, survival, and neovascularization. Previously, we have shown that receptors for CXCL-8, CXCR1, and CXCR2 are expressed on endothelial cells and CXCR2 has been shown to be a putative receptor for angiogenic chemokines. In this report, we examined whether tumor angiogenesis and growth of CXCL-8-expressing human melanoma cells are regulated in vivo by a host CXCR2-dependent mechanism. We generated mCXCR2(-/-), mCXCR2(+/-), and wild-type nude mice following crosses between BALB/c mice heterozygous for nude(+/-) and heterozygous for mCXCR2(+/-). We observed a significant inhibition of human melanoma tumor growth and experimental lung metastasis in mCXCR2(-/-) mice as compared with wild-type nude mice. Inhibition in tumor growth and metastasis was associated with a decrease in melanoma cell proliferation, survival, inflammatory response, and angiogenesis. Together, these studies show the importance of host CXCR2-dependent CXCL-8-mediated angiogenesis in the regulation of melanoma growth and metastasis.