Role of interleukin-8 in tumor growth and metastasis of human melanoma.
Expression of interleukin-8 (IL-8) by human melanoma cells correlates with their metastatic potential in vivo. Moreover, UVB irradiation of primary cutaneous melanoma induces IL-8 mRNA and protein production and increases both tumor growth and metastasis in nude mice. Although IL-8 has been shown to be an angiogenic factor, the biological consequences of increased IL-8 production by melanoma cells and the role of IL-8 in the metastatic process remains unclear. The purpose of this review is to determine the role of IL-8 in tumor growth and metastasis of human melanoma. Transfection of nonmetastatic and IL-8-negative melanoma cells with the IL-8 gene rendered them highly tumorigenic and increased their metastatic potential in nude mice. The IL-8-transfected cells displayed upregulation of MMP-2 expression and activity and increased invasiveness through Matrigel-coated filters. Activation of MMP-2 by IL-8 can enhance the invasion of host stroma by the tumor cells and increase angiogenesis and, hence, metastasis. In addition to UVB, IL-8 can also be upregulated by hypoxia conditions, suggesting that the environment plays a major role in regulating IL-8 expression and metastasis. The studies summarized in this review suggest that in melanoma, IL-8 may serve as the angiogenic factor distinguishing benign from malignant cells.
Bar-Eli
M
M
Department of Cell Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Tex. 77030, USA. mbareli@notes.mdacc.tmc.edu
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D018450:Disease Progression; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020778:Matrix Metalloproteinase 2; D008545:Melanoma / Q000098:blood supply / Q000378:metabolism / Q000556:secondary*; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009381:Neoplasms, Radiation-Induced / Q000098:blood supply / Q000378:metabolism / Q000556:secondary; D009389:Neovascularization, Pathologic / Q000209:etiology*; D012867:Skin / Q000528:radiation effects; D012878:Skin Neoplasms / Q000098:blood supply / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D014162:Transfection; D014466:Ultraviolet Rays
D016209:Interleukin-8; D009363:Neoplasm Proteins; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2