interleukin-8 and Carcinoma--Small-Cell

We studied cytokine changes after video-assisted thoracoscopic lobectomy and conventional lobectomy in patients with stage IA lung cancer.. From June, 1997, 20 consecutive patients with stage IA non small-cell lung carcinoma underwent either conventional lobectomy via an open thoracotomy (n = 10) or video-assisted thoracoscopic lobectomy (n = 10). The cytokine concentration in serum and pleural fluid were measured for 6 days postoperatively.. Interleukin-6 and interleukin-8 leads peaked at 3 h or 1 day after surgery. Cytokine levels in pleural fluid were more than 100 times higher than corresponding systemic levels. The increase of interleukin-6 in pleural fluid 3 hours after surgery was significantly smaller in video-assisted thoracoscopic lobectomy (3971 +/- 2793 pg/mL for video-assisted thoracoscopic lobectomy vs. 23274 +/- 8426 pg/mL for open lobectomy). There were no significant differences in the serum interleukin-6 and interleukin-8 concentrations between the 2 groups.. The thoracoscopic approach lessened the increase of cytokines in pleural fluid, but benefits of reduced cytokine production in video-assisted thoracoscopy remain to be clarified.

Topics: Carcinoma, Small Cell; Female; Humans; Interleukin-6; Interleukin-8; Lung Neoplasms; Male; Middle Aged; Pleural Effusion; Pneumonectomy; Thoracic Surgery, Video-Assisted

Small cell neuroendocrine carcinoma (SCNC) of the prostate is a variant form of prostate cancer that occurs de novo or as a recurrent tumor in patients who received hormonal therapy for prostatic adenocarcinoma. It is composed of pure neuroendocrine (NE) tumor cells, but unlike the scattered NE cells in benign prostate and adenocarcinoma that are quiescent, the NE cells in SCNC are highly proliferative and aggressive, causing death in months. In this study, we provide evidence that interleukin 8 (IL8)-CXCR2-P53 (TP53) signaling pathway keeps the NE cells of benign prostate and adenocarcinoma in a quiescent state normally. While P53 appears to be wild-type in the NE cells of benign prostate and adenocarcinoma, immunohistochemical studies show that the majority of the NE tumor cells in SCNC are positive for nuclear p53, suggesting that the p53 is mutated. This observation is confirmed by sequencing of genomic DNA showing p53 mutation in five of seven cases of SCNC. Our results support the hypothesis that p53 mutation leads to inactivation of the IL8-CXCR2-p53 signaling pathway, resulting in the loss of an important growth inhibitory mechanism and the hyper-proliferation of NE cells in SCNC. Therefore, we have identified potential cells of origin and a molecular target for prostatic SCNC that are very different from those of conventional adenocarcinoma, which explains SCNC's distinct biology and the clinical observation that it does not respond to hormonal therapy targeting androgen receptor signaling, which produces short-term therapeutic effects in nearly all patients with prostatic adenocarcinoma.

Topics: Adenocarcinoma; Carcinoma, Small Cell; Cell Line, Tumor; Humans; Interleukin-8; Male; Mutation; Prostatic Neoplasms; Receptors, Interleukin-8B; Signal Transduction; Tumor Suppressor Protein p53

Cyclooxygenase (COX)-2 has been implicated in tumour progression, angiogenesis and metastasis in non-small cell lung cancer (NSCLC). We speculated that inhibition of COX-2 activity might reduce expression of the pro-angiogenic factors vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) in lung cancer cells.. The levels of IL-8, VEGF and prostaglandin E2 (PGE2) were measured by ELISA. Expression of COX-1 and COX-2 was determined by Western blotting. Inhibition or knockdown of COX-2 was achieved by treating NSCLC cells with specific COX-2 inhibitor NS-398 or COX-2 siRNA, respectively.. We found that NSCLC cell lines produced more IL-8 than VEGF (p < 0.001). In contrast, small cell lung cancer (SCLC) cell lines produced more VEGF than IL-8 (p < 0.001). COX-1 was expressed in all cell lines, but COX-2 was expressed only in NSCLC cell lines. Consistent with this, PGE2 was significantly higher in NSCLC cell lines than SCLC cell lines (p < 0.001). We tested these cell lines with a potent specific COX-2 inhibitor NS-398 at concentrations of 0.02, 0.2, 2, 20 microM for 24 or 48 h. The COX-2 activity was reduced in a dose-dependent fashion as shown by reduced PGE2 production. VEGF was significantly reduced following the treatment of NS-398 in A549 (by 31%) and MOR/P (by 47%) cells lines which expressing strong COX-2, but not in H460 cell line which expressing very low COX-2. However, IL-8 was not reduced in these cell lines. To confirm these results, we knocked down COX-2 expression with COX-2 siRNA in these cell lines. VEGF was significantly decreased in A549 (by 24%) and in MOR/P (by 53%), but not in H460 whereas IL-8 was not affected in any cell line.. We conclude that NSCLC cells produce much higher levels of IL-8 than SCLC cells whereas both NSCLC and SCLC cells produce similar levels of VEGF. COX-2 is only expressed in NSCLC cells, but not in SCLC cells. VEGF is produced in both NSCLC and SCLC cells regardless of COX-2 expression. However, VEGF production is, at least partly, COX-2 dependent in NSCLC cells expressing COX-2. In contrast, IL-8 production is COX-2 independent in both NSCLC and SCLC cells. We speculate that combined targeting of COX-2 and IL-8 may be useful in the treatment of patients with NSCLC and targeting VEGF may be useful in the treatment of patients with SCLC.

Topics: Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Cell Line, Tumor; Cell Proliferation; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Dinoprostone; Disease Progression; Gene Expression Regulation, Neoplastic; Humans; Interleukin-8; Lung Neoplasms; Neoplasm Metastasis; Neovascularization, Pathologic; Vascular Endothelial Growth Factor A

In studied analyzed role of the cytokines in pathology of neoplasms of various origin the importance of these proteins in regulation of immunocompetent cells function has been described. The aim of this study was to estimate of cho sen cytokines concentration produced by peripheral blood mononuclear cells and in whole blood in patients with laryngeal carcinoma and to analyze the connection of cytokines profile with clinicopathological features. MATERIALA AND METHODS: 55 patients with squamous cell carcinoma of the larynx treated at ENT Department Medical University of Lodz between 2003-2007 were analyzed. For estimation of cytokine secretion the cultures of isolated peripheral blood mononuclear cells (T lymphocytes) and the whole blood were established. Production of cytokines in supernatants was detected by Elisa. Connections with clinicomorphological features (pT, pN, Anneroth, Batsakis i Lunas' classification) were analyzed.. Authors reported statistical correlation between chosen cytokines concentration and clinicomorphological parameters: pT and IL-2, IL-6, IL-8, TNFalpha produced by isolated cells and IL-2, IL-6, TNFa and IFNgamma in whole blood, pN and IL-8, IL-10, IFNgamma; ABL score and IL-6, TNFalpha, IFNgamma produced by isolated cells and IL-2, IL-6, IL-10, TNFalpha, IFNgamma in whole blood.. Our studied indicated the important influence of proinflammatory and regulatory cytokines produced by immunocompetent cells for course of neoplasm disease, aggressiveness and advance in laryngeal carcinoma.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Small Cell; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interferon-gamma; Interleukin-10; Interleukin-2; Interleukin-6; Interleukin-8; Laryngeal Neoplasms; Leukocytes, Mononuclear; Male; Middle Aged; Neoplasm Staging; Poland; Retrospective Studies; Tumor Necrosis Factor-alpha

We previously demonstrated the simultaneous induction of urokinase-type plasminogen activator and interleukin-8, a CXC chemokine, in doxorubicin-treated human NCI-H69 small cell lung cancer cells in which extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase might be involved. NCI-H69 cells expressed one of the receptor tyrosine kinases, c-Kit, and STI571 inhibited the cell growth and stem cell factor-induced phosphorylation of c-Kit. We therefore investigated the effects of STI571 on the expression of urokinase-type plasminogen activator and interleukin-8 in NCI-H69 cells. Microarray analysis revealed the gene induction of not only urokinase-type plasminogen activator and interleukin-8, but also early growth response-1 in STI571-treated cells. Treatment with STI571 resulted in the induction of phosphorylation of all three mitogen-activated protein kinases, such as extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase and stress-activated protein kinase/c-jun N-terminal protein kinase. U0126, an inhibitor against extracellular signal-regulated kinase 1/2, however, only inhibited the STI571-induced interleukin-8 accumulation. Urokinase-type plasminogen activator and interleukin-8 are important biological factors in tumor cell regulation; STI571 may therefore influence many aspects of tumor cell biology through inducing urokinase-type plasminogen activator and interleukin-8, in which the induction of early growth response-1 expression and extracellular signal-regulated kinase 1/2 phosphorylation might be involved.

Topics: Benzamides; Carcinoma, Small Cell; Cell Line, Tumor; Drug Screening Assays, Antitumor; Early Growth Response Protein 1; Extracellular Signal-Regulated MAP Kinases; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Imatinib Mesylate; Interleukin-8; MAP Kinase Signaling System; Oligonucleotide Array Sequence Analysis; Piperazines; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-kit; Pyrimidines; Transcriptional Activation; Urokinase-Type Plasminogen Activator

We sought to investigate the prognostic significance of nuclear factor (NF)-kappaB activity, especially nuclear RelA and IkappaB-alpha expression patterns, in non-small cell lung cancer (NSCLC).. A total of 116 patients with pathologically confirmed stage I to II NSCLC were included. Immunohistochemical analysis and electrophoretic mobility shift assays of NF-kappaB were performed to determine RelA and phosphorylated IkappaB-alpha staining, and DNA binding activity of NF-kappaB in human NSCLC. Downstream genes, including VEGF and IL-8, were also assessed. The prognostic significance of a single expression of RelA, phosphorylated IkappaB-alpha, and b-composite expressions was evaluated by Cox proportional hazard regression models and by Kaplan-Meier survival analyses. Correlation between RelA/IkappaB-alpha expression status and clinicopathological features of NSCLC was also analyzed.. NF-kappaB DNA binding activity, VEGF, and IL-8 showed correlation with nuclear RelA and cytoplasmic pIkappaB-alpha expression. Expression of nuclear RelA/NF-kappaB showed an increase in NSCLC tissue compared with adjacent normal tissue and normal lung tissue. There was a positive correlation between NF-kappaB activation (nuclear translocation of RelA) and tumor clinicopathological features such as tumor grade, including T stages, N stages, and tumor, node, metastasis system stages, smoking status, and age. Positive correlation was observed between nuclear RelA and cytoplasmic pIkappaB-alpha. Both nuclear RelA and cytoplasmic pIkappaB-alpha were associated with poor prognosis by univariate and multivariate analyses.. Nuclear RelA and cytoplasmic pIkappaB-alpha expression are associated with a poorer prognosis in NSCLC patients. In particular, composite application of these two biomarkers might be of greater value than application of a single marker to identify patients at high risk, even at an early clinical stage.

Topics: Adenocarcinoma; Apoptosis; Biomarkers, Tumor; Blotting, Western; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cell Nucleus; Cytoplasm; Electrophoretic Mobility Shift Assay; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Humans; I-kappa B Proteins; Immunoenzyme Techniques; Interleukin-8; Lung Neoplasms; Male; Middle Aged; NF-kappa B; NF-KappaB Inhibitor alpha; Prognosis; Survival Rate; Transcription Factor RelA; Vascular Endothelial Growth Factor A

We previously demonstrated the doxorubicin-induced expression of urokinase-type plasminogen activator (uPA), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha in human RC-K8 lymphoma cells and NCI-H69 small cell lung carcinoma cells in which reactive oxygen species might be involved. Amurubicin hydrochloride (AMR), a novel derivative drug of doxorubicin, was recently introduced to clinical practice for treatment of lung cancer in Japan. Therefore, we investigated the effects of AMR on the expression of uPA and chemokines in NCI-H69 cells. AMR and its active form, amurubicinol hydrochloride (AMROH), both induced the expression of uPA, IL-8 and MCP-1 in H69 cells in a dose-dependent manner. When the cultured supernatant obtained from AMR-treated H69 cells was subcutaneously injected into rabbits, migration of a significant number of eosinophils was observed around the injected site. Antigen levels of eotaxin-3, a major migration-factor of eosinophils, were increased in AMROH-treated cells in parallel with the mRNA levels. The induction was observed below the clinically achievable concentration of AMR or AMROH. Thus, the simultaneous induction of uPA, IL-8, MCP-1 and eotaxin-3 may play a role in the pharmacological action of AMR through induction of the interaction between proinflammatory cells and lung carcinoma cells.

Topics: Animals; Anthracyclines; Blotting, Northern; Carcinoma, Small Cell; Cell Line, Tumor; Cell Movement; Chemokine CCL2; Chemokine CCL26; Chemokines, CC; Culture Media, Conditioned; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Eosinophils; Gene Expression Regulation, Neoplastic; Humans; Injections, Subcutaneous; Interleukin-8; Lung Neoplasms; Rabbits; RNA, Messenger; Urokinase-Type Plasminogen Activator

Interleukin-8/CXCL8 (IL-8) is a chemokine and angiogenic factor. Recently, IL-8 was identified as an autocrine growth factor in several human cancers. Here, we investigated the expression and function of IL-8 in lung cancer cells. The expressions of IL-8 and its receptors, CXCR1 and CXCR2, were examined in a panel of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cell lines. Using reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay, we found that all NSCLC cell lines tested produced modest or high levels of IL-8 (up to 51 ng ml(-1) 10(6) cells(-1)). Expression of CXCR1 and CXCR2 was found by RT-PCR and flow cytometry in two out of three cell lines. In contrast, SCLC cell lines produced very low or undetectable levels of IL-8, but expressed CXCR1 and CXCR2. We next investigated whether IL-8 could act as an autocrine growth factor in two NSCLC cell lines (H460 and MOR/P) expressing both IL-8 and its receptors. We found that cell proliferation was attenuated by anti-IL-8 neutralising antibody to 71 and 76% in H460 and MOR/P, respectively (P<0.05). Exogenous IL-8 significantly stimulated cell proliferation in four SCLC cell lines tested in a dose-dependent fashion. Cell proliferation was increased by between 18% (P<0.05) and 37% (P<0.05). Stimulation of cell proliferation by IL-8 was also demonstrated by analysis of proliferating cell nuclear antigen expression and cell cycle in H69 cells. Furthermore, we investigated which receptor(s) mediated the mitogenic function of IL-8 in lung cancer cells. We found that cell proliferation was significantly reduced by anti-CXCR1 antibody but not by anti-CXCR2 antibody. In conclusion, IL-8 can act as an autocrine and/or paracrine growth factor for lung cancer cells, and the mitogenic function of IL-8 in lung cancer is mediated mainly by CXCR1 receptor.

Topics: Autocrine Communication; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Cell Proliferation; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Humans; Interleukin-8; Lung Neoplasms; Paracrine Communication; Receptors, Interleukin-8A; Receptors, Interleukin-8B; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Transfection; Tumor Cells, Cultured

We previously demonstrated doxorubicin-induced urokinase expression in human H69 SCLC cells by the microarray technique using Human Cancer CHIP version 2 (Takara Shuzo, Kyoto, Japan), in which 425 human cancer-related genes were spotted on glass plates (Kiguchi et al., Int J Cancer 2001;93:792-7). Microarray analysis also revealed significant induction of IL-8, a member of the CXC chemokines. We have, therefore, extended the observation by testing the effects of doxorubicin on expression of the chemokine family and provide here definitive evidence that doxorubicin induces IL-8 and MCP-1, one of the CC chemokines, at least in 2 human SCLC cells, H69 and SBC-1. IL-8 antigen levels, measured by ELISA, were markedly increased in both H69 and SBC-1 conditioned media after doxorubicin treatment, in parallel with mRNA levels; and this was dependent on the dose of doxorubicin. The ribonuclease protection assay, using a multiprobe template set for human chemokines, revealed induction of not only IL-8 but also MCP-1 in doxorubicin-treated H69 cells. MCP-1 antigen levels increased approximately 100-fold in doxorubicin-treated H69 cells. RT-PCR using specific primers for MCP-1 suggested that doxorubicin also induced MCP-1 expression in SBC-1 and SBC-3 SCLC cells. Futhermore, CAT analysis using IL-8 promoter implicated the PEA3 transcriptional factor, whose binding site was located immediately upstream of the AP-1 and NF-kappaB binding sites. Thus, it is suggested that doxorubicin induces IL-8 and MCP-1 chemokines in human SCLC cells by activating gene expression, in which at least PEA3 is involved. IL-8 and MCP-1 are major chemoattractants for neutrophils and monocytes/macrophages, respectively; therefore, extensive induction of IL-8 and MCP-1 may provoke the interaction between inflammatory/immune cells and tumor cells under doxorubicin stimulation and influence many aspects of tumor cell biology.

Topics: Antibiotics, Antineoplastic; Blotting, Northern; Carcinoma, Small Cell; Chemokine CCL2; Chloramphenicol O-Acetyltransferase; DNA Primers; Doxorubicin; Electrophoretic Mobility Shift Assay; Gene Expression Profiling; Gene Expression Regulation; Humans; Interleukin-8; Lung Neoplasms; NF-kappa B; Oligonucleotide Array Sequence Analysis; Promoter Regions, Genetic; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transcription Factor AP-1; Transcription Factors; Transcription, Genetic; Transfection; Tumor Cells, Cultured

This study was conducted to develop biologically relevant animal models of human lung cancer that are reproducible, inexpensive, and easy to perform.. Human lung adenocarcinoma (PC14PE6), bronchioloalveolar carcinoma (NCI-H358), squamous cell carcinoma (NCI-H226), poorly differentiated non-small cell lung cancer (NCI-H1299 and A549), or small cell lung cancer (NCI-H69) cells in Matrigel were injected percutaneously into the left lungs of nude mice. The growth pattern of the different lung cancer tumors was studied. For PC14PE6 and NCI-H358, the growth pattern in the subcutis and the response to paclitaxel were also studied.. As is observed for human primary lung cancer, tumors formed from a single focus of disease and progressed to a widespread and fatal thoracic process characterized by diffuse dissemination of lung cancer in both lungs and metastasis to intra- and extrathoracic lymph nodes. When the lung cancer cell lines were implanted s.c., systemic therapy with paclitaxel induced tumor regression. However, only a limited therapeutic response to paclitaxel was observed when the same cells were implanted orthotopically into the lung. Immunohistochemical analysis of tumor tissue revealed increased expression of the proangiogenic factors interleukin 8, basic fibroblast growth factor, and vascular endothelial growth factor/vascular permeability factor.. Our orthotopic models of human lung cancer confirm the "seed and soil" concept and likely provide more clinically relevant systems for the study of both non-small cell lung cancer and small cell lung cancer biology, and for characterizing novel therapeutic strategies.

Topics: Animals; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Line, Tumor; Fibroblast Growth Factor 2; Humans; Interleukin-8; Lung Neoplasms; Lymphatic Metastasis; Mice; Mice, Nude; Models, Biological; Neoplasm Metastasis; Neovascularization, Pathologic; Paclitaxel; Vascular Endothelial Growth Factor A

Soot particles, asbestos fibres and irritant gas are common air pollutants which are able to induce lung and airway pulmonary injury. The aim of this study was to investigate the effect of a simultaneous NO2 and particle or fibre exposure on the proinflammatory specific mRNA expression and protein secretion of human alveolar macrophages (AM) in comparison to only particle or fibre exposed AM. AM were simultaneously exposed to FR 101, P 90, TiO2 or Chrysotile B at a concentration of 100 microg/10(6) cells and to NO2 at a concentration of 1.0 ppm for 30 min. Particle or fibre exposure of the AM was continued in humidified air at 5% CO2 and 37 degrees C for an additional hour (harvesting of total RNA) or additional 7 hrs (harvesting of culture supernatant). The mRNA expression of the proinflammatory cytokines IL-1beta, IL-6, IL-8 and TNF-alpha of NO2-particle/fibre co-exposed AM and only particle or fibre exposed AM was detected using specific RT-PCR. IL-1beta-, IL-6-, IL-8- and TNF-alpha-specific protein secretion was measured by ELISA. Cytotoxicity was detected by lactatedehydrogenase quantification in the culture supernatant. We observed an increased IL-1beta-, IL-6-, IL-8- and TNF-alpha-specific mRNA expression of particle or fibre exposed AM, which was decreased after an additional NO2 exposure. Also the particle or fibre exposure induced significant increase in IL-1beta-, IL-6-, IL-8 and TNF-alpha-release of AM which was decreased after an additional NO2 exposure (p <0.031). The relative cytotoxicity of the NO2-particle/fibre co-exposure was higher than the particle or fibre induced cytotoxicity, but mostly <10%. Therefore it is concluded that particle or fibre exposure may result in an increase in proinflammatory cytokine release by AM, which may be decreased by toxic NO2 due to the oxidative potential (e.g. lipidperoxydation) of this irritant gas. Particle, asbestos fibre and irritant gas exposure may induce airway and pulmonary injury by the activation of AM and consecutive proinflammatory cytokine release.

Topics: Aged; Air Pollutants; Asbestos, Serpentine; Asthma; Bronchial Neoplasms; Bronchoalveolar Lavage Fluid; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Cells, Cultured; Cytokines; Drug Synergism; Female; Gene Expression Regulation; Humans; Inflammation; Interleukin-1; Interleukin-6; Interleukin-8; Irritants; Lung Neoplasms; Macrophages, Alveolar; Male; Middle Aged; Nitrogen Dioxide; Particle Size; RNA, Messenger; Titanium; Tumor Necrosis Factor-alpha

Cellular immunity plays a major role in controlling human papilloma virus infection and development of cervical carcinoma. Mononuclear cell infiltration possibly due to the action of chemokines becomes prominent in the tumor tissue. In fact, the macrophage chemoattractant protein-1, MCP-1, was detected in cervical squamous cell carcinoma in situ, whereas absent in cultured cells. From this, unknown environmental factors were postulated regulating chemokine expression in vivo. In this study, we show high CD40 expression on cervical carcinoma cells and CD40 ligand (CD40L) staining on attracted T cells in tumor tissue, suggesting a paracrine stimulation mechanism via CD40L-CD40 interactions. We therefore investigated chemokine synthesis in nonmalignant and malignant human papilloma virus-positive cell lines after CD40L exposure. Constitutive expression of MCP-1, MCP-3, RANTES, and IFN-gamma-inducible protein-10 was almost undetectable in all cell lines tested. CD40L was able to induce MCP-1 production; however, despite much higher CD40 expression in malignant cells, MCP-1 induction was significantly lower compared with nontumorigenic cells. After sensitization with IFN-gamma, another T cell-derived cytokine showing minimal effects on CD40 expression levels, CD40 ligation led to a more than 20-fold MCP-1 induction in carcinoma cell lines. An even stronger effect was observed for IFN-gamma-inducible protein-10. Our study highlights the synergism of T cell-derived mediators such as CD40L and IFN-gamma for chemokine responses in cervical carcinoma cells, helping to understand the chemokine expression patterns observed in vivo.

Topics: Carcinoma, Small Cell; CD40 Antigens; CD40 Ligand; Cell Line, Transformed; Cell Transformation, Neoplastic; Chemokine CCL2; Chemokine CXCL10; Chemokines; Chemokines, CXC; Drug Synergism; Female; Humans; Interferon-gamma; Interleukin-8; Keratinocytes; Ligands; Membrane Glycoproteins; NF-kappa B; Papillomaviridae; Papillomavirus Infections; Protein Binding; Tumor Cells, Cultured; Uterine Cervical Neoplasms

We examined interleukin-8 (IL-8) production in 17 lung cancer cell lines, IL-8 expression in tumor specimens and IL-8's contribution to tumor-induced angiogenesis in vivo. Eight of 13 non-small cell lung cancer cell lines constitutively produced high levels of IL-8. Four small cell lung cancer cell lines produced little or no IL-8. Immunohistochemical analysis of transbronchial biopsy specimens revealed IL-8 staining within adenocarcinomas (22/32), squamous cell carcinomas (12/21) and large cell carcinomas (2/3), but not within most small cell carcinomas (1/22). Anti-IL-8 antisera blocked tumor angiogenesis by two IL-8 producing cell lines in a mouse model.

Topics: Adenocarcinoma; Animals; beta-Galactosidase; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Division; Interleukin-8; Lung Neoplasms; Mice; Neoplasm Transplantation; Neovascularization, Pathologic; Transplantation, Heterologous; Tumor Cells, Cultured