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)

Peptide regulatory factors, i.e. cytokines, are released spontaneously or upon induction by melanoma cells in culture. Among these cytokines there are factors such as Il-1, IL-6, IL-8, IL-10 as well as TGF-beta 1 which are basically acting as immunoregulatory molecules. However, their contribution to an augmentation and/or suppression of local or systemic immune response against melanoma cells in situ has not yet been elucidated. On the other hand, some of these molecules, e.g. IL-6 and TGF-beta 1, are growth inhibitors, especially in the early phases of melanoma development. During tumor progression, resistance to the inhibitory effect of these cytokines seems to take place. Whether this resistance is due to an excessive production of these cytokines or a downregulation or blockade of receptors is still controversial. The aberrant expression of bFGF in melanoma cells explains how melanoma cells in vitro and probably also in vivo acquire growth autonomy and the capacity of metastasis formation. The expression of bFGF by human melanoma cells and its activity as autocrine growth regulator imply that agents which interfere with heparin-binding growth factors such as Suramin or pentosan sulfate may be of clinical usefulness. Additionally, these latter agents have been shown to be potent anti-angiogenic factors. Their clinical efficacy, however, has to be established in phase I and II studies.
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PMID:Production of polypeptide regulatory factors by human melanoma cells. 772 36

This review concentrates on growth autonomy of tumor cells in relation to tumor progression. Human malignant melanoma serves as an example for progressive growth factor independence at subsequent stages of tumor progression. Mechanisms by which malignant cells acquire growth factor independence are discussed. In melanoma, deregulation of growth regulatory pathways has been described on four levels: 1) aberrant production of autocrine growth factors that substitute for exogenous growth factors (basic fibroblast growth factor [bFGF]); 2) alterations in the response to negative autocrine growth factors (interleukin [IL]-6 and transforming growth factor [TGF]-beta); 3) overexpression of epidermal growth factor receptors (EGF-R); and 4) alterations of cellular protooncogenes involved in signal transduction (RAS, MYB) and growth suppression (p53). In addition to bFGF and IL-6, multiple other growth factor genes are activated in malignant melanoma cells but not normal melanocytes. These include both chains of platelet-derived growth factor (PDGF), TGF-alpha, IL-1, IL-8, and tumor necrosis factor (TNF)-alpha. Of these, PDGF-B has been investigated in more detail. Melanoma-derived PDGF clearly does not act in a direct autocrine mode, but has important paracrine effects on normal tissue constituents, notably fibroblasts and endothelial cells, that are essential for tumor development in vivo. It is speculated that other melanoma-derived growth factors with as yet undefined functions similarly exert such paracrine or 'indirect' autocrine effects that cannot be sufficiently addressed in studies on cultured cells.
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PMID:Growth factor independence and growth regulatory pathways in human melanoma development. 828 9

The host-tumor interaction may play an important role in determining tumor progress. Recent studies have shown that this interaction can be influenced by the release of soluble factors by tumor cells and tumor-infiltrating lymphocytes (TIL). The aim of our study is to characterize the nature of cytokines and growth factors and their relationship to the cellular infiltrates in 16 patients with ovarian cancer using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. Total RNA from 20 malignant and 10 benign specimens were used to assay for expression of 12 cytokines. Additionally, monoclonal antibodies (MAbs) were used to detect T cells, CD4+ helper and CD8+ cytotoxic/suppressor T-cell subtypes, B cells, and macrophages. Our results showed the expression of transforming growth factor-beta1 (TGF-beta1), interleukin-10 (IL-10), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in 19, 17, and 10 malignant specimens, P < .001, .001, and .05, respectively. Other cytokines such as interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), TNF-beta/LT, IL-2, and IL-6 were expressed in a few cases, and IL-1alpha and IL-4 expression were not detected. The benign samples did not express IL-10, but GM-CSF, TGF-beta1, and IL-8 were expressed in one, one, and four specimens, respectively. Interestingly, in four cases in which samples from the primary and relapse tumors were available for analysis, the tumors in relapse showed a significant increase for TGF-beta1 (P < .05) and a decreased trend in IL-10 mRNA levels. The source of these factors was tumor cells as detected immunohistochemically. This combined alteration of TGF-beta1 and IL-10 was associated with a significant reduction in number of TIL in general, and CD8+ and macrophages in particular (P = .036 and .049, respectively). Our findings suggest the important role of certain soluble factors in the complex process of tumor progression. Furthermore, understanding the tumor-host relationship and the factors influencing the interaction may be helpful in developing effective and innovative treatment methods.
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PMID:Tumor-host interaction: analysis of cytokines, growth factors, and tumor-infiltrating lymphocytes in ovarian carcinomas. 904 97

We compared the cytogenetic pattern of 20 different primary tumor cell cultures (PTCC) of renal cell carcinoma (RCC) to their cytokine secretion and oncogene expression. High secretion of IL-6 (gene locus on chromosome 7p21-p14) was correlated with the gain of an additional chromosome 7. Structural changes involving chromosome 5q22, the site of the GM-CSF gene, were matched with the high secretion of GM-CSF in PTCC. No such association was found for beta 2-microglobulin, TGF-beta 1, TNF-alpha, IL-8, and oncogenes, such as c-fos, c-myc, and pan-ras. Our approach may be useful in simultaneously analyzing several factors contributing to tumor progression and may contribute to understanding the multistep development of RCC.
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PMID:Comparison of cytogenetics, cytokine secretion, and oncogene expression in primary cultures of renal carcinoma cells. 926 Jun 6

A role in tumor progression has been proposed for transforming growth factor-beta 1 (TGF beta 1) and interleukin (IL)-8 as well as for IL-1, which itself induces the production of TGF beta 1 and IL-8 in many cell types. TGF beta 1 and IL-8 production and their regulation by IL-1 in five non-small-cell (NSC) lung tumor cell lines were evaluated. Moreover, their levels were evaluated in 29 NSC lung tumors. All cell lines constitutively produced TGF beta 1, and three produced IL-8. After IL-1 beta treatment, TGF beta 1 production was upregulated in two cell lines, whereas IL-8 production was markedly upregulated in two, induced in one, and unmodified in two. In tumors, the levels of TGF beta 1, IL-8, and IL-1 beta were higher than in normal counterparts (p < 0.001), and a positive correlation between IL-8 and IL-1 beta levels (p < 0.001) was found. TGF beta 1, IL-8, and IL-1 beta mRNA expression was examined in 12 tumors. TGF beta 1 mRNA was detected in all cases, IL-8 mRNA in 7, and IL-1 beta MRNA was undetectable. TGF beta 1, IL-8, and IL-1 beta immunoreactivity was then studied by immunohistochemistry. TGF beta 1 and IL-8 immunoreactivity was observed in neoplastic cells; IL-1 beta immunoreactivity was observed in mononuclear cells. In conclusion, in tumors IL-1 beta levels positively correlated with those of IL-8, and IL-1 beta as well as TGF beta 1 and IL-8 levels were significantly higher than in normal tissues.
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PMID:Transforming growth factor beta 1, interleukin-8 and interleukin-1, in non-small-cell lung tumors. 931 21

Leukocyte infiltration and necrosis are two biological phenomena associated with the development of neovascularization during the malignant progression of human astrocytoma. Here, we demonstrate expression of interleukin (IL)-8, a cytokine with chemotactic and angiogenic properties, and of IL-8-binding receptors in astrocytoma. IL-8 expression is first observed in low grade astrocytoma in perivascular tumor areas expressing inflammatory cytokines. In glioblastoma, it further localizes to oxygen-deprived cells surrounding necrosis. Hypoxic/anoxic insults on glioblastoma cells in vitro using anaerobic chamber systems or within spheroids developing central necrosis induced an increase in IL-8 messenger RNA (mRNA) and protein expression. mRNA for IL-8-binding chemokine receptors CXCR1, CXCR2, and the Duffy antigen receptor for chemokines (DARC) were found in all astrocytoma grades by reverse transcription/PCR analysis. In situ hybridization and immunohistochemistry localized DARC expression on normal brain and tumor microvascular cells and CXCR1 and CXCR2 expression to infiltrating leukocytes. These results support a model where IL-8 expression is initiated early in astrocytoma development through induction by inflammatory stimuli and later in tumor progression increases due to reduced microenvironmental oxygen pressure. Augmented IL-8 would directly and/or indirectly promote angiogenesis by binding to DARC and by inducing leukocyte infiltration and activation by binding to CXCR1 and CXCR2.
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PMID:Upregulation of interleukin 8 by oxygen-deprived cells in glioblastoma suggests a role in leukocyte activation, chemotaxis, and angiogenesis. 933 59

Progression of cervical cancer is associated with excessive circulating levels of cytokines, which are known to be modulators of tumor angiogenesis. The concentrations of cytokines and growth factors were assayed using enzyme-linked immunosorbant assays in the serum of 61 women in various stages of cancer [stage 0 (n = 6), stage I (n = 15), stage II (n = 15), stage III (n = 15), and stage IV (n = 10)] and of 20 healthy control subjects. Our results indicated that b-FGF and TNF-beta levels were significantly elevated in stage I, and serum levels of TGF-beta and IL-7 were elevated in stages II-IV of invasive carcinoma. Our experimental subjects had significantly increased serum levels of IL-6, GM-CSF, and angiogenin in stages I-IV of cervical cancer, and TNF-alpha serum levels were elevated in all stages of invasive carcinoma. The serum levels of IL-8 and IL-10 were elevated only in stages II-III, and the levels of IL-2 were elevated in stages III-IV. The serum levels of IL-1 alpha and IL-1 beta remained unaltered in all stages of cancer progression. Progression of cervical cancer is associated with increased serum levels of angiogenin, IL-2, IL-6, IL-7, IL-8, IL-10, b-FGF TNF-alpha, TGF-beta, TNF-beta, and GM-CSF during different stages, all of which have the potential to be angiogenic amplifiers.
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PMID:Circulating serum levels of cytokines and angiogenic factors in patients with cervical cancer. 954 28

Here, we report the functional expression of CD40 on human malignant melanomas (MMs). Comparison of tumor specimen from MM precursor lesions, primary tumors, and metastases revealed that CD40 surface expression is down-regulated during tumor progression. CD40 expression was confirmed in 7 human MM cell lines established from immunogenic primary tumors or metastases, whereas 11 cell lines established from advanced stages were CD40 negative. CD40 expression could be enhanced in CD40-positive MM by stimulation with IFN-gamma and tumor necrosis factor-alpha but not by interleukin (IL)-1beta or CD40 triggering. CD40 ligation on MM by CD40L-transfected murine L-cells or by a soluble CD40L fusion protein up-regulated their expression of intercellular adhesion molecule-1 and MHC class I and class II molecules and their secretion of IL-6, IL-8, tumor necrosis factor-a, and granulocyte macrophage colony-stimulating factor and also induced a rapid activation of the transcription factor nuclear factor kappaB. Furthermore, CD40 ligation of a HLA-A2+, MelanA/MART1+ MM cell line enhanced its susceptibility to specific lysis by a HLA-A2-restricted, MelanA/MART-1-specific CTL clone. Finally, CD40 ligation induced growth inhibition and apoptosis in MM. These results indicate that CD40-CD40L interactions may play an important role in augmenting antitumor immunity and inducing apoptosis in some CD40-positive immunogenic human MMs.
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PMID:Stimulation of CD40 on immunogenic human malignant melanomas augments their cytotoxic T lymphocyte-mediated lysis and induces apoptosis. 1009 61

Angiogenesis is essential for tumor progression and metastasis. It is mediated by the release of angiogenic factors by the tumor or host. We analyzed the expression of angiogenic factors by the prostate cancer cell line LNCaP and two derived variants, in vitro and in vivo, to determine whether metastatic cell lines express higher levels of these factors. The production of three angiogenic factors, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and interleukin 8 (IL-8), by LNCaP and its variants, LNCaP-LN3 (highly metastatic) and LNCaP-Pro5 (slightly metastatic), was measured by ELISA. VEGF, bFGF, and IL-8 mRNA expression was determined in vitro by Northern blot analysis. VEGF mRNA expression was determined in vivo by in situ hybridization. VEGF and flk-1 protein expression and microvessel density of LNCaP cell tumors were quantified by immunohistochemistry. In vitro, VEGF production by LNCaP-LN3 (3.15+/-0.04 pg/ml/10(3) cells) was significantly higher than those of both LNCaP (2.38+/-0.34 pg/ml/10(3) cells) and LNCaP-Pro5 (1.67+/-0.37 pg/ml/10(3) cells; P = 0.049 and 0.001, respectively). None of the three cell lines produced detectable levels of bFGF or IL-8 in vitro. In vivo, LNCaP-LN3 tumors exhibited higher levels of VEGF mRNA and protein (152.2+/-28.5 and 200.5+/-28.3) and of flk-1 protein (156.5+/-20.6) and had higher microvessel density (16.4+/-4.2) than either LNCaP tumors (89+/-17.5, 173.3+/-23.0, 124.6+/-21.6, and 12.4+/-3.5, respectively) or LNCaP-Pro5 tumors (63+/-14.7, 141.2+/-38.1, 126.1+/-20, and 5.8+/-2.2, respectively). In conclusion, metastatic human prostate cancer cells exhibited enhanced VEGF production and tumor vascularity compared with prostate cancer cells of lower metastatic potential. Thus, VEGF may play an important role in prostate cancer metastasis.
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PMID:Highly metastatic human prostate cancer growing within the prostate of athymic mice overexpresses vascular endothelial growth factor. 1021 13

Hepatocyte growth factor (HGF), also known as scatter factor (SF), is known to act on cancer cells as well as endothelial cells and stimulate angiogenesis, thus playing an unwanted role in the development and progression of cancer. The current study examined the effects of a newly discovered HGF variant, NK4, on angiogenesis in vitro. Chemically generated NK4 (from recombinant human HGF/SF) was found to be able to inhibit HGF-induced activation (tyrosine phosphorylation) of the HGF/SF receptor cMET but was itself unable to activate cMET. Furthermore, NK4 was demonstrated to inhibit tubule formation from human umbilical vein endothelial cells that was induced by both HGF/SF and a HGF/SF-producing fibroblast (MRC5). Under the same settings, NK4 failed to increase tubular formation. NK4 had no effects on interleukin 8- and vascular endothelial growth factor-induced tubule formation. Using computer-assisted motion analysis, it was further shown that NK4 inhibited HGF-induced migration of human umbilical vein endothelial cells in a migration assay and in an endothelial wounding assay. These data show that NK4 is a complete antagonist to HGF. It inhibits HGF-induced endothelial movement and tubule formation. Thus, NK4 may have an important bearing on the control of cancer progression through its role in angiogenesis. Additional in vivo studies are warranted.
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PMID:Antagonistic effect of NK4, a novel hepatocyte growth factor variant, on in vitro angiogenesis of human vascular endothelial cells. 1058 89


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