Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor angiogenesis, a major requirement for tumor outgrowth and metastasis formation, is regulated by pro- and anti-angiogenic factors. We have studied the expression of a panel of angiogenic factors, and of the angiogenesis inhibitor angiostatin, in a panel of human melanoma cell lines giving rise to xenografts with different vascular densities. Angiogenic-factor expression was analyzed in vitro (cell lines) and in vivo (xenografts), both at mRNA (RT-PCR and Northern blot) and at protein level (ELISA and Western blot). In vitro angiostatin generation was assessed by Western-blot analysis. Expression of bFGF and VEGF was clearly correlated with a high degree of vascularization, confirming the importance of these factors for tumor angiogenesis. In addition, there was exclusive or elevated in vitro expression of angiogenic factors IL-8, PDGF-AB, and, to a lesser extent, midkine in cell lines that formed highly vascularized tumors. A similar angiogenic-factor-expression pattern was found in the corresponding xenografts, with the exception of VEGF. In most cell lines, this factor had low expression in vitro which was strongly enhanced in vivo. Although all 8 melanoma cell lines were able to excise the angiostatin fragment from the plasminogen parent molecule in vitro, cell lines BLM and M14 showed the most potent angiostatin generation. In vitro angiostatin generation by cell lysates prepared from melanoma xenografts was comparable in all xenograft types. Thus, in our model system we found no correlation between angiostatin generation and vascular density. Our study has limited the number of pro-angiogenic factors that may be involved in melanoma angiogenesis, and provides evidence for the notion that regulation of tumor angiogenesis is dependent on multiple factors. Inhibition of angiogenesis for therapeutic purposes, therefore, should preferably not concentrate on a single factor.
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PMID:Angiogenic balance in human melanoma: expression of VEGF, bFGF, IL-8, PDGF and angiostatin in relation to vascular density of xenografts in vivo. 1084 89

The tumor microenvironment is thought to play an important role in invasion and metastasis. Previously, we have shown that signaling from melanoma cells can alter the gene expression profiles of fibroblasts in vitro and in vivo. To investigate whether the capacity to signal fibroblasts and alter host gene expression profiles is correlated to the invasive potential of specific human melanoma cell lines, we assayed changes in gene expression of fibroblasts when cocultured with the human melanoma cell lines BLM, MV3, A2058, SK-mel28 and WM164. Results indicated that the gene expression of key chemokines and cytokines, such as IL-1B, IL-8, IL-6 and CCL2/MCP1, was significantly upregulated in fibroblasts cocultured with the invasive melanoma lines BLM and MV3 compared to fibroblasts cocultured with noninvasive WM164 cells. The results were verified by quantitative RT-PCR as well as by protein assay and supported by immunohistochemistry of human invasive melanoma. Furthermore, a role for fibroblast-secreted IL-1B in the invasion of melanoma was demonstrated in vitro, where siRNA silencing of IL-1B in melanoma-stimulated fibroblasts resulted in a diminution of melanoma invasion. Although CCL2/MCP1, a chemoattractant for macrophages, was shown to be upregulated in fibroblasts cocultured with metastatic melanoma cell lines, immunohistochemical analysis of human melanoma also indicated CCL2/MCP1 production associated with the melanoma. In summary, these experiments indicate that the invasiveness of melanoma can partly be correlated to its ability to stimulate host stromal fibroblasts to give rise to the secretion of chemokines that generate a microenvironment that is conductive for melanoma invasion and metastasis.
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PMID:The invasive potential of human melanoma cell lines correlates with their ability to alter fibroblast gene expression in vitro and the stromal microenvironment in vivo. 1956 39

Tumour microenvironment plays a critical role in cell invasion and metastasis. To investigate the role of cancer-associated fibroblasts (CAFs) in melanoma cell invasiveness, we used 3D spheroid invasion assay. The effect of conditioned media from normal fibroblasts and CAFs cultivated alone or co-cultivated with melanoma cells on BLM or A2058 melanoma spheroid invasion was analysed. We found that conditioned media from CAFs and CAFs co-cultured with melanoma cells, especially, promote invasion and migration, without significant effect on melanoma cell proliferation. We further analysed the expression of pro-invasive cytokines IL-8 and IL-6 in media and found that melanoma cells are dominant producers of IL-8 and fibroblasts are dominant producers of IL-6 in 2D monocultures, while co-cultivation of CAFs with melanoma cells induces production/secretion of IL-6 and IL-8 into the media. The analyses of IL-6 levels in 3D cultures and human melanoma samples, however, revealed that at least in some cases IL-6 is also produced directly by melanoma cells. Analysis of the role of IL-6 and IL-8 in CAF-induced melanoma invasion, using neutralising antibodies, revealed that simultaneous blocking of IL-6 and IL-8 is sufficient to fully inhibit CAF-induced human melanoma cell invasiveness. In summary, these experiments indicate the important role of CAFs and IL-8 and IL-6 cytokines in melanoma cell invasiveness.
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PMID:Simultaneous blocking of IL-6 and IL-8 is sufficient to fully inhibit CAF-induced human melanoma cell invasiveness. 2710 77