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)

The four main cell functions, proliferation, apoptosis, differentiation and migration, are tightly regulated by external signals that initiate intracellular signal transduction pathways and determine the cellular behaviour. The concentration and composition of such external signals are at least important for the decision of cells as to which function has to be executed. Interleukin-8 is a well known inducing signal for neutrophil granulocyte migration, while the epidermal growth factor is an inducing signal for breast carcinoma cell migration. Depending on the concentrations of interleukin-8, the neutrophil granulocytes are capable of migration. However, at high concentration of interleukin-8 the migratory activity of each single cell is reduced, indicating that high concentrations of the chemokine inhibit migration and promote the performance of other cell functions. Concerning breast carcinoma cells, the epidermal growth factor is not only an inducer of migration but also an inhibitor of proliferation. These two examples provide evidence for a dose dependent action of external signals for several cell functions in parallel. This versatility of the effects of one ligand might be based on several intracellular signal transduction pathways that are turned on. For the dose-dependent differences of the effect of interleukin-8 we propose a two wheel model of an inositolphosphate-mediated, ATP-independent release of calcium from intracellular stores and a cyclic AMP-mediated, ATP-dependent uptake of calcium into the endoplasmatic reticulum.
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PMID:Lessons from tumor and immunocompetent cells. The quantitative engagement of ligand-receptor interactions modulates stop-and-go behavior as well as proliferation. 1118 27

The scenario of multiple genetic and epigenetic alterations found in gastric carcinoma differs depending upon the two histological types, indicating that well differentiated or intestinal type and poorly differentiated or diffuse type gastric carcinomas have different genetic pathways. Cancer-stromal interaction through growth factor/cytokine receptor system which plays a central role in invasion and metastasis, is also different between the two types of stomach cancer. The majority of gastric carcinoma exhibit co-expression of IL-8 and its two receptors that evidently confer tumor angiogenesis. IL-8 increases the expression of EGF receptor, VEGF and IL-8 itself by tumor cells themselves, whereas IL-8 decreases expression of E-Cadherin, associated with increase in expression and activity of MMP-9 by tumor cells. These findings overall suggest that IL-8 produced by gastric cancer cells is used for sustained angiogenesis and tissue invasion and metastasis via autocrine/paracrine manners. On the other hand, co-expression of osteopontin (OPN) and CD44v9 in tumor cells correlates well with the degree of lyiphatic vessel invasion or long distant lymph node metastasis in diffuse type gastric carcinoma, indicating that mutual interaction between OPN and CD44v9 on the tumor cells is implicated in lymphogenous metastasis. In addition to these factors, tumor invasion and metastasis requires telomere maintenance regulated by telomerase activity. The human telomerase catalytic subunit, hTERT, is strongly expressed in almost all primary tumors and nodal metastasis.
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PMID:Molecular aspects of invasion and metastasis of stomach cancer. 1121 48

Leukaemia inhibitory factor (LIF) and interleukin (IL)-8 possess activities which may contribute to the development of carcinomas. LIF can stimulate proliferation of some tumour cell lines and IL-8 is angiogenic. Using semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), we measured the expression of LIF and IL-8 mRNA in cultured normal keratinocytes (NKC) and the malignant carcinoma cells lines A431, SiHa, HeLa, and in biopsies of basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and normal skin. Protein expression for LIF was assessed by immunohistochemistry in the biopsies. LIF mRNA expression was increased significantly (P < 0.01) in all carcinoma lines, except SiHa, compared with NKC but the IL-8 mRNA expression in carcinoma cell lines was similar to that in NKC. Expression of LIF mRNA was elevated in BCC and SCC compared with normal skin, but a significant difference was observed only between SCC and normal skin (P < 0.01). Both BCC and SCC showed significantly greater expression of IL-8 compared with normal skin (P < 0.01). There was no correlation between LIF and IL-8 mRNA expression either in BCCs or in SCCs. Immunoreactivity for LIF was absent throughout BCC and SCC, however, normal epidermis surrounding the tumour stained positive, as in normal skin. These data may suggest a role for LIF and IL-8 in the development of skin carcinomas, but without co-ordinate regulation of these two cytokines in this process.
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PMID:Leukaemia inhibitory factor and interleukin-8 expression in nonmelanoma skin cancers. 1126 Jan 84

PTHrP (parathyroid hormone-related protein) overexpression by prostate carcinoma cells has been implicated in tumor progression. Although the biological effects of PTHrP can be mediated by the G-protein-coupled PTH/PTHrP receptor, PTHrP also has intracrine actions mediated by a nuclear localization sequence at residues 87-107. We investigated the effect of PTHrP transfection and treatment on production by prostate carcinoma cells of IL (interleukin)-8, which can regulate prostate cancer growth by angiogenic activity and growth-promoting effects. Six prostate cancer cell lines exhibited constitutive expression of PTHrP and IL-8 that were significantly correlated (r = 0.93; P < 0.01). We transfected wild-type and mutant PTHrP into these cells. Wild-type PTHrP1-173 and PTHrP33-173 lacking the PTH/PTHrP receptor-binding domain induced a 3-fold stimulation of IL-8 production but not production of another angiogenic factor, vascular endothelial growth factor. Transfection of the COOH-terminal truncation mutant PTHrP1-87 induced a 5-fold simulation of IL-8 and a 3-fold increase in IL-8 mRNA. Cells transfected with PTHrP1-87 and 1-173 also showed increased cell proliferation. In contrast, exogenous PTHrP1-34 and 1-86 peptides did not significantly affect IL-8 production; moreover, PTHrP-neutralizing antibodies did not inhibit the production of IL-8 by transfected PTHrP. Additional transfection studies with progressively COOH-terminally truncated PTHrP1-87 defined a 23-amino acid sequence, PTHrP65-87, required for PTHrP1-87 to robustly stimulate IL-8 in prostate cancer cells. Confocal microscopy and immunoassay demonstrated PTHrP1-87 nuclear localization. Our results demonstrate that PTHrP acts to induce IL-8 production in prostate cancer cells via an intracrine pathway independent of its classical nuclear localization sequence. This novel pathway could mediate the effects of PTHrP on the progression of prostate cancer.
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PMID:Parathyroid hormone-related protein induces interleukin 8 production by prostate cancer cells via a novel intracrine mechanism not mediated by its classical nuclear localization sequence. 1128 Jul 99

Data presented in this report indicate short-term in vitro treatment of nonmetastatic MCF-7 breast carcinoma cells with the chemotherapeutic agents-, Adriamycin and/or 5-fluoro-2'-deoxyuridine (FUdR), induced changes in the expressed phenotype. Cells treated sequentially with Adriamycin and FUdR expressed a metastatic phenotype. The results also show short-term exposure of MCF-7 cells to either Adriamycin or FUdR rapidly increases, in a dose-dependent manner, the release of the angiogenic cytokine, interleukin-8(IL-8), which is released at consistently higher levels in metastatic cell lines. Cell populations surviving a single treatment with either one or both of these chemotherapeutic agents continue to stably release IL-8. Survivors of sequential treatment with Adriamycin and FUdR (MCF-7 A/F) release the most IL-8 and express the greatest phenotypic variance from the parental, MCF-7 cells. Parental MCF-7 cells and MCF-7 A/F cells both form primary tumors when used in an orthotopic tumor model; however, the MCF-7 A/F tumors have a more rapid initial growth phase in situ and give rise to spontaneous lung metastases within 10 weeks. A cell line that is established from lung metastases releases more IL-8, has a higher cloning efficiency, and forms looser colonies in monolayer than do their parental cells. These experiments indicate the in vitro exposure of tumor cells to chemotherapeutic agents either selects more aggressive cells or enhances the metastatic potential of the surviving cells.
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PMID:Progression and enhancement of metastatic potential after exposure of tumor cells to chemotherapeutic agents. 1130 58

Lung cancer is commonly associated with multiorgan metastasis, and bone is a frequent metastatic site for lung cancer. Nevertheless, no bone metastasis model of lung cancer with multiorgan dissemination is available, which could provide opportunity to study the molecular pathogenesis. We examined the abilities of eight human lung cancer cell lines injected intravenously into natural killer (NK) cell-depleted SCID mice to generate metastatic nodules in bone and multiple organs, and explored the correlation of the parathyroid hormone-related protein (PTHrP) with the bone metastasis. Although all the small-cell carcinoma cell lines (SBC-5, SBC-3, SBC-3/ADM, H69, H69/VP) formed metastatic nodules in multiple organs (liver, kidney, and lymph nodes), only SBC-5 cells reproducibly developed bone metastases. Squamous cell carcinoma (RERF-LC-AI) cells metastasized mainly into the liver and kidneys, whereas adenocarcinoma (PC-14, A549) mainly produced colonies in the lungs. As assessed by X-ray photography, the osteolytic bone metastases produced by SBC-5 cells were detected as early as on day 28, and all recipient mice developed bone metastasis by day 35. The expression of PTHrP in eight cell lines was directly correlated with the formation of bone metastasis. No correlation was observed between the formation of bone metastasis and the expression of other metastasis-related cytokines (IL-1, IL-6, IL-8, IL-10, IL-11, TNF-alpha, VEGF, M-CSF). Consistent with the formation of bone metastasis by SBC-5 cells, the levels of PTHrP and calcium in the mouse serum were increased in a time-dependent manner, suggesting that PTHrP produced by human lung cancer may play a crucial role in the formation of bone metastasis and hypercalcemia. These findings indicate that a bone metastasis model of SBC-5 cells may be useful for clarifying the molecular aspects of the metastatic processes in different organ microenvironments and the development of therapeutic modalities for lung cancer patients with bone metastases.
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PMID:Bone metastasis model with multiorgan dissemination of human small-cell lung cancer (SBC-5) cells in natural killer cell-depleted SCID mice. 1141 46

We established a new cell line, NUGC-3P4T, with high peritoneal metastatic disseminating potential in nude mice. NUGC-3P4T cells were derived from the human gastric carcinoma line NUGC-3, which has low capacity for peritoneal dissemination. NUGC-3P4T cells developed peritoneal dissemination in 10 / 10 (100%) mice, whereas the parental NUGC-3 cells developed dissemination in 1 / 5 (20.0%) mice. The metastatic foci in the peritoneum showed essentially the same histological appearance as those induced by parental cells. The tumorigenicity, the motile activity and the adhesive activity to the laminin of NUGC-3P4T cells were stronger than those of NUGC-3 cells. Production of IL-8 was significantly higher in NUGC-3P4T than in NUGC-3. cDNA macroarrays analysis showed that a variety of cytokines, interleukins, and other immunomodulators and their receptors were up- or down-regulated at the mRNA level in NUGC-3P4T cells, compared with NUGC-3 cells. Thus, this unique cell line and in vivo model might be useful to study the biology of peritoneal dissemination of human gastric cancer.
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PMID:A novel experimental mouse model of peritoneal dissemination of human gastric cancer cells: analysis of the mechanism of peritoneal dissemination using cDNA macroarrays. 1147 25

Angiogenesis, an essential step in the development of neoplasia, is a complex process that involves the interaction of tumor cells with stromal cells. Tumor-associated macrophages (TAMs) can participate in the induction of tumor angiogenesis and are thought to be of prognostic value in some neoplasms. We have investigated how macrophages contribute to angiogenesis in head-and-neck squamous-cell carcinoma (HNSCC) and have found that tumor cells attract monocytes and activate them to secrete angiogenic factors. The attraction of macrophages was due to the secretion of monocyte chemotactic protein-1 and TGF-beta1 by tumor cells, while tumor production of TGF-beta1 was responsible for activating macrophages. In addition, activated macrophages produced cytokines that acted in a paracrine fashion by secreting both TNF-alpha and IL-1, which in turn stimulated tumor cells to secrete increased levels of IL-8 and VEGF. These data demonstrate that TAMs play an important role in the in vivo induction of angiogenesis in HNSCC and suggest that anti-angiogenic therapies for HNSCC and perhaps other neoplasms must include strategies that will block the ability of tumor cells to recruit macrophages into the tumor micro-environment.
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PMID:Paracrine angiogenic loop between head-and-neck squamous-cell carcinomas and macrophages. 1151 37

The anti-tumour effect of the angiogenic inhibitor TNP470, sigma-(chloro-acetyl-carbamoyl) fumagillol, a synthetic analogue of fumagillin, was studied in vitro and in vivo using KB cells, one of the human head and neck carcinoma cell lines that produce interleukin(IL)-8. In the in vitro study, the combination treatment of TNP470 and anti-IL-8 antibody significantly reduced the proliferation of KB cells. In the in vivo studies, TNP470 administration by any route (intratumoral: i.t., intraperitoneal: i.p., intravenous: i.v.) reduced the tumour volume significantly, compared to the control group. Among the groups administered TNP470, the anti-tumour effect was strongest in the it group. Furthermore, the concurrent treatment of anti-IL-8 antibody and TNP470 also maximally reduced the tumour volume. The combination therapy of TNP470 and anti-IL-8 antibody was very effective. These results suggest that combination therapy of TNP470 and anti-IL-8 antibody could be beneficial for solid tumours, such as head and neck cancer.
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PMID:The inhibitory effects of TNP470 on tumour growth of head and neck carcinoma cell producing interleukin-8. 1166 92

A novel human thyroid papillary carcinoma cell line (FB-2) has been established and characterized. FB-2 cells harbor the RET/PTC1 chimeric oncogene in which the RET kinase domain is fused to the H4 gene. FB-2 cells neither formed colonies in semisolid media nor induced tumors after heterotransplant into severe combined immunodeficient mice. However, HMGI(Y), HMGI-C and c-myc genes, which are associated to thyroid cell transformation, were abundantly expressed in FB-2 cells but not in normal thyroid cells. FB-2 cells only partially retained the differentiated thyroid phenotype. In fact, the PAX-8 gene, which codes for a transcriptional factor required for thyroid cell differentiation, was expressed, while thyroglobulin, TSH-receptor and thyroperoxidase genes were not. Moreover, FB-2 cells produced high levels of interleukin (IL)-6 and IL-8.
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PMID:Establishment of a non-tumorigenic papillary thyroid cell line (FB-2) carrying the RET/PTC1 rearrangement. 1180 85


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