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)

Cytokines appear to play an important role in the development and progression of epithelial tumors. Cultured normal human thyroid follicular cells constitutively release high levels of interleukin-6 (IL-6) and IL-8, together with low to moderate levels of transforming growth factor-alpha (TGF-alpha) and TGF-beta. IL-6 appears to play multiple functions in thyroid physiology and disease. Because certain data indicate an inverse relationship between IL-6 production and epithelial tumor aggressiveness, we used both tissue culture methods and histochemical techniques to search for possible alterations of cytokine expression in thyroid carcinomas. As compared to cultures from normal tissue and well-differentiated carcinoma, production of IL-6 was strongly down-regulated in cultures derived from undifferentiated carcinoma. In contrast, levels of IL-8, TGF-alpha, and TGF-beta produced by neoplastic TFC were similar to those produced by normal cells. Actually, production of TGF-alpha was slightly enhanced in cultures from well-differentiated carcinoma. Immunoassay results were confirmed by reverse transcriptase-PCR analysis. Immunohistochemistry of human thyroid carcinomas (n = 99) and normal thyroid tissue (n = 85) showed that immunoreactive IL-6 was strongly diminished in undifferentiated forms (n = 34) and slightly reduced in well-differentiated carcinoma (n = 65). In agreement with the in vitro results, TGF-alpha expression was significantly increased in neoplastic thyrocytes, as compared to their normal counterpart. The results indicate that, as in the mammary and salivary glands, down-regulation of IL-6 expression may represent a marker of undifferentiated thyroid carcinoma.
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PMID:Reduced expression of interleukin 6 in undifferentiated thyroid carcinoma: in vitro and in vivo studies. 951 26

High levels of prostaglandins are produced in human oropharyngeal carcinoma (OPC). Five human OPC cell lines tested expressed both isoforms of cyclooxygenases (COX). The pan-COX inhibitor ketorolac continuously and significantly decreased PGE(2) production and IL-6 and IL-8 levels in all OPC cell lines tested, but did not affect IL-1alpha, GM-CSF levels, or in vitro tumor cell growth. In contrast, ketorolac reduced OPC growth in vivo. The OPC cell lines used express the IL-6 receptor, and IL-6 stimulation of these cells causes transduction to occur via STAT3 pathway activation. Coincubation with OPC cell lines with conditioned medium from a TPA-exposed HL-60 cells stimulated growth proportional to the IL-6 levels measured in the conditioned medium. This growth effect was specifically inhibited by anti-IL-6 antibody. These results are consistent with cytokine products of inflammatory cells having paracrine growth effects on OPC. If chronic inflammation plays a role in promoting the development of OPC, this mechanism may also apply to other epithelial tumor systems modulated by COX activity.
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PMID:Cyclooxygenase regulates human oropharyngeal carcinomas via the proinflammatory cytokine IL-6: a general role for inflammation? 1092 84

Cellular senescence suppresses cancer by arresting cell proliferation, essentially permanently, in response to oncogenic stimuli, including genotoxic stress. We modified the use of antibody arrays to provide a quantitative assessment of factors secreted by senescent cells. We show that human cells induced to senesce by genotoxic stress secrete myriad factors associated with inflammation and malignancy. This senescence-associated secretory phenotype (SASP) developed slowly over several days and only after DNA damage of sufficient magnitude to induce senescence. Remarkably similar SASPs developed in normal fibroblasts, normal epithelial cells, and epithelial tumor cells after genotoxic stress in culture, and in epithelial tumor cells in vivo after treatment of prostate cancer patients with DNA-damaging chemotherapy. In cultured premalignant epithelial cells, SASPs induced an epithelial-mesenchyme transition and invasiveness, hallmarks of malignancy, by a paracrine mechanism that depended largely on the SASP factors interleukin (IL)-6 and IL-8. Strikingly, two manipulations markedly amplified, and accelerated development of, the SASPs: oncogenic RAS expression, which causes genotoxic stress and senescence in normal cells, and functional loss of the p53 tumor suppressor protein. Both loss of p53 and gain of oncogenic RAS also exacerbated the promalignant paracrine activities of the SASPs. Our findings define a central feature of genotoxic stress-induced senescence. Moreover, they suggest a cell-nonautonomous mechanism by which p53 can restrain, and oncogenic RAS can promote, the development of age-related cancer by altering the tissue microenvironment.
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PMID:Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. 1905 74

Saliva testing, a non-invasive alternative to serum testing, may be an effective modality for diagnosis and for prognosis prediction of oral cancer, as well as for monitoring post therapy status, by measuring specific salivary macromolecules, examining proteomic or genomic targets such as enzymes, cytokines, growth factors, metalloproteinases, endothelin, telomerase, cytokeratines, mRNA's and DNA transcripts. Salivary analysis has been shown to be a useful diagnostic tool also for distant malignancies such as breast cancer. In recent years, significant alterations have been demonstrated in the saliva of oral cancer patients in the epithelial tumor markers--Cyfra 21-1, TPS and CA12, various oxidative stress-related salivary parameters as ROS and RNS, biochemical and immunological parameters as IGF and MMP's and RNA transcripts of IL8, IL-1B, DUSP1, HA3, OAZ1, S100P, and SAT. Collectively these accumulated data are predicted to alter the field of oral cancer diagnosis by employing highly sensitive new tools which will enable both medical professionals and the patients themselves to monitor their saliva for diagnosis and prognosis prediction, as they relate to oral cancer. At this point however, the aim of salivary analysis is mainly for screening which may be helpful in the future.
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PMID:Saliva as a tool for oral cancer diagnosis and prognosis. 1982 59

The switch of tumor cells from an epithelial to a mesenchymal-like phenotype [designated as epithelial-to-mesenchymal transition (EMT)] is known to induce tumor cell motility and invasiveness, therefore promoting metastasis of solid carcinomas. Although multiple studies have focused on elucidating the signaling events that initiate this phenotypic switch, there has been so far no characterization of the pattern of soluble mediators released by tumor cells undergoing EMT, and the potential impact that this phenotypic switch could have on the remodeling of the tumor microenvironment. Here we show that induction of EMT in human carcinoma cells via overexpression of the transcription factor Brachyury is associated with enhanced secretion of multiple cytokines, chemokines, and angiogenic factors and, in particular, with the induction of the IL-8/IL-8R axis. Our results also indicate the essential role of interleukin 8 (IL-8) signaling for the acquisition and/or maintenance of the mesenchymal and invasive features of Brachyury-overexpressing tumor cells and show that IL-8 secreted by tumor cells undergoing EMT could potentiate tumor progression by inducing adjacent epithelial tumor cells into EMT. Altogether, our results emphasize the potential role of EMT in the modulation of the tumor microenvironment via secretion of multiple soluble mediators and suggest that IL-8 signaling blockade may provide a means of targeting mesenchymal-like, invasive tumor cells.
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PMID:IL-8 signaling plays a critical role in the epithelial-mesenchymal transition of human carcinoma cells. 2165 78

The phenomenon of epithelial-mesenchymal transition (EMT) has gained attention in the field of cancer biology for its potential contribution to the progression of carcinomas. Tumor EMT is a phenotypic switch that promotes the acquisition of a fibroblastoid-like morphology by epithelial tumor cells, resulting in enhanced tumor cell motility and invasiveness, increased metastatic propensity and resistance to chemotherapy, radiation and certain small-molecule-targeted therapies. Tumor cells undergoing EMT are also known to increase the secretion of specific factors, including cytokines, chemokines and growth factors, which could play an important role in tumor progression. This review summarizes the current knowledge on the secretory properties of epithelial tumor cells that have undergone an EMT, with an emphasis on the potential role of the IL-8-IL-8 receptor axis on the induction and/or maintenance of tumor EMT and its ability to remodel the tumor microenvironment.
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PMID:Influence of IL-8 on the epithelial-mesenchymal transition and the tumor microenvironment. 2276 69