interleukin-8 and Tongue-Neoplasms

It is now possible to identify several key factors that determine biological characteristics of squamous cell cancer of the head and neck: genes p53, p16, cyclin D1, P13-K/Akt connected with metastasis proteins (proteases, proteins mesenchymal cells, cell adhesion molecules chemokines), angiogenesis factors (VEGF, PDGF, FGF, TGF-alpha and TGF-beta), IL-8; epidermal growth factor receptors. An important role of tumor cells plays microenvironment. Of course the above mentioned is only a small part of the factors that determine the livelihoods and the activity of cancer cells. All of these factors are potential predictors of the effectiveness of radiation and chemoradiation treatment and actively studied in recent decades.

Topics: Adult; Aged; Aged, 80 and over; Angiogenic Proteins; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma, Squamous Cell; Chemokines; Chemoradiotherapy; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p16; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-8; Male; Middle Aged; Neoplasm Proteins; Neoplasm Staging; Phosphatidylinositol 3-Kinases; Predictive Value of Tests; Prognosis; Prospective Studies; Proto-Oncogene Proteins c-akt; Retrospective Studies; Risk Factors; Tongue Neoplasms; Treatment Outcome; Tumor Suppressor Protein p53

The present study aimed to explore the clinical significance of neutrophils infiltration and carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1) expression in the tongue squamous cell carcinoma (TSCC), and to probe the possible relationship between them.. Tissue microarray and immunohistochemistry were used to detect neutrophils density and CEACAM1 expression in 74 cases of primary TSCC specimens and 17 cases of corresponding peritumoral tissues. The relationship of CEACAM1 expression and neutrophils density with clinicopathologic parameters and cancer-related survival of TSCC patients were evaluated. The correlation between CEACAM1 expression and neutrophils density was also evaluated. Real-time quantitative transcription polymerase chain reaction (qRT-PCR) was used to explore the possible molecular mechanisms between CEACAM1 expression and neutrophils infiltration.. Immunohistochemistry evaluation revealed that there was more neutrophils infiltration in TSCC tissues than in peritumoral tissues. High neutrophil density was associated with LN metastasis (P=0.01), higher clinical stage (P=0.037) and tumor recurrence (P=0.024). CEACAM1 overexpression was also associated with lymph node metastasis (P=0.000) and higher clinical stage (P=0.001). Survival analysis revealed that both neutrophils infiltration and CEACAM1 overexpression were associated with poorer cancer-related survival of TSCC patients (P<0.05), and neutrophils infiltration was an independent prognostic factor for TSCC (P<0.05). Furthermore, overexpression of CEACAM1 was correlated with more neutrophils infiltration in TSCC tissues (P<0.01). qRT-PCR results showed that CEACAM1-4L can upregulate the mRNA expression of IL-8 and CXCL-6, which were strong chemotactic factors of neutrophils.. Our results demonstrated that more neutrophils infiltration and overexpression of CEACAM1 were associated with poor clinical outcomes in TSCC tissues. Overexpression of CEACAM1 on tumor cells correlated with more neutrophils infiltration to some extent through upregulating mRNA expression of IL-8 and CXCL-6.

Topics: Adult; Aged; Alternative Splicing; Antigens, CD; Carcinoma, Squamous Cell; Cell Adhesion Molecules; Chemokine CCL2; Chemokine CXCL6; Female; Gene Expression; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Interleukin-8; Lewis X Antigen; Male; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Neutrophil Infiltration; Neutrophils; Tongue Neoplasms; Transfection

Production of IL-8 primarily promotes angiogenic responses in cancer cells, which lead to favorable disease progression. Suppressing this production may, therefore, be a significant therapeutic intervention in targeting tumor angiogenesis. This study aimed to evaluate the reduction effects of xanthones in cancer cell lines. Nine known prenylated xanthones (1-9), isolated from the pericarp of Garcinia mangostana Linn (GML), were tested for their ability to suppress IL-8 (interleukin-8) of the SP-C1 (Supri's Clone 1) tongue cancer cell line. Of these compounds, 8-hydroxycudraxanthone-G (4) suppressed IL-8 within 48 hours. This is the first report of 8-hydroxycudraxanthone G suppressing the production of IL-8 (45% at 15.7 microg/mL in 48 hours). These results suggest that the prolonged suppression of IL-8 production by cancer cell lines is concerned in the anti-cancer activity of 8-hydroxycudraxanthone.

Topics: Antineoplastic Agents, Phytogenic; Carcinoma, Squamous Cell; Cell Line, Tumor; Drug Screening Assays, Antitumor; Garcinia mangostana; Humans; Interleukin-8; Plants, Medicinal; Tongue Neoplasms; Xanthones

Worldwide, the incidence of oral tongue cancer is on the rise, adding to the existing burden due to prevailing low survival and high recurrence rates. This study uses high-throughput expression profiling to identify candidate markers of resistance/response in patients with oral tongue cancer. Analysis of primary and post-treatment samples (12 tumor and 8 normal) by the Affymetrix platform (HG U133 plus 2) identified 119 genes as differentially regulated in recurrent tumors. The study groups had distinct profiles, with induction of immune response and apoptotic pathways in the non-recurrent and metastatic/invasiveness pathways in the recurrent group. Validation was carried out in tissues by Quantitative Real-Time PCR (QPCR) (n=30) and immunohistochemistry (IHC) (n=35) and in saliva by QPCR (n=37). The markers, COL5A1, HBB, IGLA and TSC individually and COL5A1 and HBB in combination had the best predictive power for treatment response in the patients. A subset of markers identified (COL5A1, ABCG1, MMP1, IL8, FN1) could be detected in the saliva of patients with oral cancers with their combined sensitivity and specificity being 0.65 and 0.87 respectively. The study thus emphasizes the extreme prognostic value of exploring markers of treatment resistance that are expressed in both tissue and saliva.

Topics: Adult; ATP Binding Cassette Transporter, Subfamily G, Member 1; ATP-Binding Cassette Transporters; Biomarkers, Tumor; Carcinoma, Squamous Cell; Collagen Type V; Fibronectins; Follow-Up Studies; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genetic Markers; Humans; Interleukin-8; Male; Matrix Metalloproteinase 1; Middle Aged; Mouth Mucosa; Neoplasm Recurrence, Local; Predictive Value of Tests; Reference Values; Reproducibility of Results; Saliva; Tongue Neoplasms

To investigate the roles of inflammatory factors and nuclear factor kappa B (NF-kappaB) signal pathway in metastasis of oral squamous cell carcinoma.. The oral squamous cell carcinoma cell lines with highly metastasis potential (Tb) and lower metastasis potential (Tca8113) were used in this study. The levels of NF-kappaB activity in oral squamous cell carcinoma cell lines were determined by Western blotting and luciferase reporter assay. pBalphabe-IkappaBalpha-SR expression vector or NF-kappaB inhibitor pyrolidinedithiocarbamate (PDTC) was used to inhibit NF-kappaB, and cell migration was examined by transwell assay. The secretion of tumor necrosis factor-alpha (TNF-alpha), IL-1alpha, IL-6, IL-8 and GM-CSF proinflammatory cytokines was determined by ELISA when Tb cells were transfected with pBalphabe-SR-IkappaBalpha or treated with PDTC.. Western blotting showed that the levels of phosphorIkappaBalpha and phosphor-p65 were highly expressed in Tb cells. Tb cells had high level of constitutive NF-kappaB activity and were more sensitive to TNF-alpha. The migration of highly metastatic Tb cells, either transfected with dominant-negative mutant inhibitor pBalphabe-SR-IkappaBalpha or treated with PDTC, was suppressed when determined by transwell assay. The secretion of proinflammatory cytokines, including TNF-alpha, IL-1alpha, IL-6, IL-8 and granulocyte-macrophage colony stimulating factor (GM-CSF), was inhibited by pBalphabe-SR-IkappaBalpha transfection or PDTC treatment.. The inflammatory factors such as TNF-alpha could promote oral squamous cell carcinoma cell metastasis via NF-kappaB signal pathway.

Topics: Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cytokines; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; I-kappa B Proteins; Interleukin-1alpha; Interleukin-6; Interleukin-8; NF-kappa B; NF-KappaB Inhibitor alpha; Phosphorylation; Proline; Signal Transduction; Thiocarbamates; Tongue Neoplasms; Transcription Factor RelA; Tumor Necrosis Factor-alpha

The head and neck/oral squamous cell carcinoma (HNOSCC) is a diverse group of cancers, which develop from many different anatomic sites and are associated with different risk factors and genetic characteristics. The oral tongue squamous cell carcinoma (OTSCC) is one of the most common types of HNOSCC. It is significantly more aggressive than other forms of HNOSCC, in terms of local invasion and spread. In this study, we aim to identify specific transcriptomic signatures that associated with OTSCC.. Genome-wide transcriptomic profiles were obtained for 53 primary OTSCCs and 22 matching normal tissues. Genes that exhibit statistically significant differences in expression between OTSCCs and normal were identified. These include up-regulated genes (MMP1, MMP10, MMP3, MMP12, PTHLH, INHBA, LAMC2, IL8, KRT17, COL1A2, IFI6, ISG15, PLAU, GREM1, MMP9, IFI44, CXCL1), and down-regulated genes (KRT4, MAL, CRNN, SCEL, CRISP3, SPINK5, CLCA4, ADH1B, P11, TGM3, RHCG, PPP1R3C, CEACAM7, HPGD, CFD, ABCA8, CLU, CYP3A5). The expressional difference of IL8 and MMP9 were further validated by real-time quantitative RT-PCR and immunohistochemistry. The Gene Ontology analysis suggested a number of altered biological processes in OTSCCs, including enhancements in phosphate transport, collagen catabolism, I-kappaB kinase/NF-kappaB signaling cascade, extracellular matrix organization and biogenesis, chemotaxis, as well as suppressions of superoxide release, hydrogen peroxide metabolism, cellular response to hydrogen peroxide, keratinization, and keratinocyte differentiation in OTSCCs.. In summary, our study provided a transcriptomic signature for OTSCC that may lead to a diagnosis or screen tool and provide the foundation for further functional validation of these specific candidate genes for OTSCC.

Topics: Adult; Aged; Aged, 80 and over; Base Sequence; Biomarkers; Carcinoma, Squamous Cell; Case-Control Studies; Collagen; DNA Primers; Female; Gene Expression Profiling; Humans; Immunohistochemistry; Interleukin-8; Male; Matrix Metalloproteinase 9; Middle Aged; Oligonucleotide Array Sequence Analysis; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Tongue Neoplasms

Matrix metalloproteinase-1 (MMP-1) and interleukin-8 (IL-8) play an important role in cancer development and metastasis. There is a single nucleotide polymorphism (SNP) located in the promoter region of MMP-1 and IL-8 that regulates gene expression. MMP-1 -1607 2G/2G and IL-8 -251 A/A genotypes enhance transcriptional activity and may be associated with increased risk in malignant tumors. We therefore evaluated the impact of these SNPs in tongue squamous cell carcinoma (SCC).. In this study, we genotyped 69 tongue SCC patients. The expression of MMP-1 and IL-8 in tongue SCC patients was analyzed by immunohistochemistry.. We found a significant difference in IL-8 A/A genotypes with nodal recurrence (P=0.0068). An analysis of disease-free survival rates showed that the presence of both MMP-1 2G/2G and IL-8 A/A genotypes was associated with a particularly poor prognosis (P=0.0032) and was an independent prognostic factor (P=0.001). The expression of MMP-1 was significantly correlated with the frequency of MMP-1 2G/2G genotypes (P=0.049).. These results suggest that SNP in the promoter region of MMP-1 and IL-8 plays an important role in tumor progression and recurrence through its expression in tongue SCC.

Topics: Aged; Alleles; Carcinoma, Squamous Cell; Disease-Free Survival; Female; Gene Frequency; Genotype; Humans; Immunoenzyme Techniques; Interleukin-8; Male; Matrix Metalloproteinase 1; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Prognosis; Promoter Regions, Genetic; Tongue; Tongue Neoplasms

Previous work from our laboratory has demonstrated overexpression of chemokines in head and neck cancer, and the utility of targeting CXCL5 for tumor therapy in a preclinical model. In the present study, we investigated the contribution of a related chemokine, CXCL8, to cellular properties associated with tumor progression, namely cell growth and motility. Expression of CXCL8 was detectable in multiple squamous carcinoma cell lines, indicating a possible role in pathogenesis. Overexpression of CXCL8 in HN4 primary tumor cells with low endogenous CXCL8 levels was found to increase cell growth, as judged by cell counting and MTT assays. Conversely, RNAi-mediated knockdown of CXCL8 expression in HN12 cells, derived from a synchronous metastasis and which express high levels of this chemokine, resulted in a decrease in proliferation. Similarly, overexpression of CXCL8 enhanced migration of HN4 cells, while suppression of CXCL8 inhibited HN12 cell migration and invasion through a basement membrane substitute. Taken together, these findings support the hypothesis that CXCL8 affects multiple processes involved in tumor progression and identify CXCL8 as a potential therapeutic target, similar to CXCL5.

Topics: Blotting, Western; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cell Proliferation; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-8; Male; Neoplasm Invasiveness; Neoplasm Proteins; Reverse Transcriptase Polymerase Chain Reaction; Tongue Neoplasms; Tumor Cells, Cultured

BRAK/CXCL14 is a CXC chemokine constitutively expressed at the mRNA level in certain normal tissues but absent from many established tumor cell lines and human cancers. Although multiple investigators cloned BRAK, little is known regarding the physiologic function of BRAK or the reason for decreased expression in cancer. To understand the possible significance associated with loss of BRAK mRNA in tumors, we examined the pattern of BRAK protein expression in normal and tumor specimens from patients with squamous cell carcinoma (SCC) of the tongue and used recombinant BRAK (rBRAK) to investigate potential biological functions. Using a peptide-specific antiserum, abundant expression of BRAK protein was found in suprabasal layers of normal tongue mucosa but consistently was absent in tongue SCC. Consistent with previous in situ mRNA studies, BRAK protein also was expressed strongly by stromal cells adjacent to tumors. In the rat corneal micropocket assay, BRAK was a potent inhibitor of in vivo angiogenesis stimulated by multiple angiogenic factors, including interleukin 8, basic fibroblast growth factor, and vascular endothelial growth factor. In vitro, rBRAK blocked endothelial cell chemotaxis at concentrations as low as 1 nmol/L, suggesting this was a major mechanism for angiogenesis inhibition. Although only low affinity receptors for BRAK could be found on endothelial cells, human immature monocyte-derived dendritic cells (iDCs) bound rBRAK with high affinity (i.e., K(d), approximately 2 nmol/L). Furthermore, rBRAK was chemotactic for iDCs at concentrations ranging from 1 to 10 nmol/L. Our findings support a hypothesis that loss of BRAK expression from tumors may facilitate neovascularization and possibly contributes to immunologic escape.

Topics: Carcinoma, Squamous Cell; Cell Line; Chemokines, CXC; Chemotactic Factors; Cornea; Dendritic Cells; Fibroblast Growth Factor 2; Humans; Interleukin-8; Neovascularization, Pathologic; Recombinant Proteins; RNA, Messenger; Tongue Neoplasms; Vascular Endothelial Growth Factor A

Retinoids have shown great promise as chemopreventive against the development of squamous cell carcinomas of the upper aerodigestive tract. However, the exact mechanism by which they block new tumors from arising is unknown. Here, we report that 13-cis- and all-trans-retinoic acid, used at clinically achievable doses of 10(-6) mol/L or less, can directly and specifically affect cell lines cultured from oral squamous cell carcinomas, inducing them to switch from an angiogenic to an anti-angiogenic phenotype. Although retinoic-acid-treated and untreated tumor cells make the same amount of interleukin-8, the major inducer of neovascularization produced by such tumor lines, they vary in production of inhibitory activity. Only the retinoic-acid-treated cells produce a potent angio-inhibitory activity that is able to block in vitro migration of endothelial cells toward tumor cell conditioned media and to halt neovascularization induced by such media in the rat cornea. Anti-angiogenic activity is induced in the tumor cells by low doses of retinoids in the absence of toxicity with a kinetics that suggest that it could be contributing to the effectiveness of the retinoids as chemopreventive agents.

Topics: Animals; Breast Neoplasms; Carcinoma, Squamous Cell; Colonic Neoplasms; Cornea; Endothelium, Vascular; Female; Fibrosarcoma; Humans; Interleukin-8; Keratinocytes; Neovascularization, Pathologic; Neovascularization, Physiologic; Neutralization Tests; Phenotype; Rats; Rats, Inbred F344; Tongue Neoplasms; Transforming Growth Factor beta; Tretinoin; Tumor Cells, Cultured