Host CXCR2-dependent regulation of melanoma growth, angiogenesis, and experimental lung metastasis.
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.
Singh
Seema
S
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5845, USA.
Varney
Michelle
M
Singh
Rakesh K
RK
D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008545:Melanoma / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D023063:Receptors, Interleukin-8B / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics
D016209:Interleukin-8; D023063:Receptors, Interleukin-8B