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Erschienen in: Medical Oncology 4/2012

01.12.2012 | Original Paper

Single-nucleotide polymorphisms of integrins are associated with the risk and lymph node metastasis of oral squamous cell carcinoma

verfasst von: Xiang-Rui Ma, Hui Cheng, Xiao-Yi Wang, Hao Liu, Dan Zhao

Erschienen in: Medical Oncology | Ausgabe 4/2012

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Abstract

Integrins mediate cell-extracellular matrix (ECM) interaction and play a critical role in cell proliferation, migration, survival, and invasion. Polymorphisms of the Integrin gene can alter integrin protein expression, which may further increase the risk of malignancies or cause poor clinical outcomes. The aim of this study was to investigate the potential associations of single-nucleotide polymorphisms (SNPs) of the integrin gene with the susceptibility and clinicopathologic parameters of oral squamous cell carcinoma (OSCC). Two hundred patients with OSCC and 200 healthy volunteers were recruited. Five SNPs of Integrin genes were analyzed by polymerase chain reaction–restriction fragment length polymorphism genotyping. Their correlations with OSCC risk and clinical tumor characteristics were evaluated. The AT genotype of rs3809865 and GC genotype of rs1190271 increased the risk of OSCC by 2.1-fold (95% confidence interval 1.323–3.829, P = 0.004) and 2.85-fold (95% confidence interval 1.583–5.138, P < 0.01), respectively. Cases with AT genotype of rs3809865 and GC genotype of rs11902171 were prone to have regional lymph nodes metastasis (P < 0.01). The SNPs of rs3809865 and rs1190271 might contribute to the prediction of susceptibility and lymph node metastasis of OSCC, which should be thought as a diagnostic marker and a potential therapeutic target.
Literatur
2.
Zurück zum Zitat Kim M, Carman CV, Springer TA. Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. J Science. 2003;301(5640):1720–5.CrossRef Kim M, Carman CV, Springer TA. Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. J Science. 2003;301(5640):1720–5.CrossRef
3.
Zurück zum Zitat Janes SM, Watt FM. New roles for integrins in squamous-cell carcinoma. J Nature Reviews Cancer. 2006;6(3):175–83.CrossRef Janes SM, Watt FM. New roles for integrins in squamous-cell carcinoma. J Nature Reviews Cancer. 2006;6(3):175–83.CrossRef
4.
Zurück zum Zitat Kanemoto T, et al. Identification of an amino acid sequence from the laminin A chain that stimulates metastasis and collagenase IV production. Proc Natl Acad Sci USA. 1990;87(6):2279–83.PubMedCrossRef Kanemoto T, et al. Identification of an amino acid sequence from the laminin A chain that stimulates metastasis and collagenase IV production. Proc Natl Acad Sci USA. 1990;87(6):2279–83.PubMedCrossRef
5.
Zurück zum Zitat Mizejewski GJ. Role of integrins in cancer: survey of expression patterns. Proc Soc Exp Biol Med. 1999;222:124–38.PubMedCrossRef Mizejewski GJ. Role of integrins in cancer: survey of expression patterns. Proc Soc Exp Biol Med. 1999;222:124–38.PubMedCrossRef
6.
Zurück zum Zitat Gomez M, Cano A. Expression of β1 integrin receptors transformed mouse epidermal keratinocytes: upregulation of α5β1 in spindle carcinoma cells. Mol Carcinogen. 1995;12:153–65.CrossRef Gomez M, Cano A. Expression of β1 integrin receptors transformed mouse epidermal keratinocytes: upregulation of α5β1 in spindle carcinoma cells. Mol Carcinogen. 1995;12:153–65.CrossRef
7.
Zurück zum Zitat Kurokawa A, et al. Diagnostic value of integrin alpha3, beta4, and beta5 gene expression levels for the clinical outcome of tongue squamous cell carcinoma. Cancer. 2008;112:1272–81.PubMedCrossRef Kurokawa A, et al. Diagnostic value of integrin alpha3, beta4, and beta5 gene expression levels for the clinical outcome of tongue squamous cell carcinoma. Cancer. 2008;112:1272–81.PubMedCrossRef
8.
Zurück zum Zitat Ohara T, et al. Integrin expression levels correlate with invasion, metastasis and prognosis of oral squamous cell carcinoma. Pathol Oncol Res. 2009;15(3):429–36.PubMedCrossRef Ohara T, et al. Integrin expression levels correlate with invasion, metastasis and prognosis of oral squamous cell carcinoma. Pathol Oncol Res. 2009;15(3):429–36.PubMedCrossRef
9.
Zurück zum Zitat Gonzales M, et al. A cell signal pathway involving laminin-5, alpha3beta1 integrin, and mitogen-activated protein kinase can regulate epithelial cell proliferation. Mol Biol Cell. 1999;10(2):259–70.PubMed Gonzales M, et al. A cell signal pathway involving laminin-5, alpha3beta1 integrin, and mitogen-activated protein kinase can regulate epithelial cell proliferation. Mol Biol Cell. 1999;10(2):259–70.PubMed
10.
Zurück zum Zitat Chen CZ, et al. MicroRNAs modulate hematopoietic lineage differentiation. Science. 2004;303:83–6.PubMedCrossRef Chen CZ, et al. MicroRNAs modulate hematopoietic lineage differentiation. Science. 2004;303:83–6.PubMedCrossRef
11.
Zurück zum Zitat Fazi F, et al. A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBP alpha regulates human granulopoiesis. Cell. 2005;123:819–31.PubMedCrossRef Fazi F, et al. A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBP alpha regulates human granulopoiesis. Cell. 2005;123:819–31.PubMedCrossRef
12.
Zurück zum Zitat Chen JF, et al. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet. 2006;38:228–33.PubMedCrossRef Chen JF, et al. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet. 2006;38:228–33.PubMedCrossRef
13.
Zurück zum Zitat He L, et al. A microRNA polycistron as a potential human oncogene. Nature. 2005;435:828–33.PubMedCrossRef He L, et al. A microRNA polycistron as a potential human oncogene. Nature. 2005;435:828–33.PubMedCrossRef
14.
Zurück zum Zitat Chen JM, et al. A systematic analysis of disease-associated variants in the 3 regulatory regions of human protein coding genes I: general principles and overview. Hum Genet. 2006;120:1–21.PubMedCrossRef Chen JM, et al. A systematic analysis of disease-associated variants in the 3 regulatory regions of human protein coding genes I: general principles and overview. Hum Genet. 2006;120:1–21.PubMedCrossRef
15.
Zurück zum Zitat Brendle A, et al. Polymorphisms in predicted microRNA-binding sites in integrin genes and breast cancer: ITGB4 as prognostic marker. Carcinogenesis. 2008;29(7):1394–9.PubMedCrossRef Brendle A, et al. Polymorphisms in predicted microRNA-binding sites in integrin genes and breast cancer: ITGB4 as prognostic marker. Carcinogenesis. 2008;29(7):1394–9.PubMedCrossRef
16.
Zurück zum Zitat Sobin LH, Wittekind Ch, editors. UICC, TNM classification of malignant tumors. 6th ed. New York: Wiley-Liss; 2002. Sobin LH, Wittekind Ch, editors. UICC, TNM classification of malignant tumors. 6th ed. New York: Wiley-Liss; 2002.
17.
Zurück zum Zitat Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedCrossRef Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedCrossRef
18.
Zurück zum Zitat Greenlee RT, Murray T, Bolden S, Wingo P. Cancer statistics. CA Cancer J Clin. 2000;50:7–33.PubMedCrossRef Greenlee RT, Murray T, Bolden S, Wingo P. Cancer statistics. CA Cancer J Clin. 2000;50:7–33.PubMedCrossRef
19.
Zurück zum Zitat Hood JD, et al. Role of integrins in cell invasion and migration. Nat Rev Cancer. 2002;2:91–100.PubMedCrossRef Hood JD, et al. Role of integrins in cell invasion and migration. Nat Rev Cancer. 2002;2:91–100.PubMedCrossRef
20.
Zurück zum Zitat Esquela-Kerscher A, et al. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6:259–69.PubMedCrossRef Esquela-Kerscher A, et al. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6:259–69.PubMedCrossRef
21.
22.
Zurück zum Zitat Chen J, et al. Association between ITGA2 C807T polymorphism and gastric cancer risk. World J Gastroenterol. 2011;17(23):2860–6.PubMed Chen J, et al. Association between ITGA2 C807T polymorphism and gastric cancer risk. World J Gastroenterol. 2011;17(23):2860–6.PubMed
23.
Zurück zum Zitat Jones J, Watt F, Speight PM. Changes in the expression of alpha a v integrins in oral squamous cell carcinomas. J Oral Pathol Med. 1997;26:63–8.PubMedCrossRef Jones J, Watt F, Speight PM. Changes in the expression of alpha a v integrins in oral squamous cell carcinomas. J Oral Pathol Med. 1997;26:63–8.PubMedCrossRef
24.
Zurück zum Zitat Regezi JA, Ramos DM, Pytela R, Dekker NP, Jordan CK. Tenascin and β6 integrin are overexpressed in floor of mouth in situ carcinomas and invasive squamous cell carcinomas. J Oral Oncol. 2004;38(4):332–6.CrossRef Regezi JA, Ramos DM, Pytela R, Dekker NP, Jordan CK. Tenascin and β6 integrin are overexpressed in floor of mouth in situ carcinomas and invasive squamous cell carcinomas. J Oral Oncol. 2004;38(4):332–6.CrossRef
25.
Zurück zum Zitat Jones J, Sugiyama M, Speight PM, Watt FM. Restoration of alpha v beta 5 integrin expression in neoplastic keratinocytes results in increased capacity for terminal differentiation and suppression of anchorage-independent growth. Oncogene. 1996;12(1):119–26.PubMed Jones J, Sugiyama M, Speight PM, Watt FM. Restoration of alpha v beta 5 integrin expression in neoplastic keratinocytes results in increased capacity for terminal differentiation and suppression of anchorage-independent growth. Oncogene. 1996;12(1):119–26.PubMed
26.
Zurück zum Zitat Ramos DM, et al. Expression of integrin beta 6 enhances invasive behavior in oral squamous cell carcinoma. Matrix Biol. 2002;21(3):297–307.PubMedCrossRef Ramos DM, et al. Expression of integrin beta 6 enhances invasive behavior in oral squamous cell carcinoma. Matrix Biol. 2002;21(3):297–307.PubMedCrossRef
27.
Zurück zum Zitat Munger JS, et al. The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell. 1999;96:319–28.PubMedCrossRef Munger JS, et al. The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell. 1999;96:319–28.PubMedCrossRef
28.
Zurück zum Zitat Li P, et al. Chemokine receptor 7 promotes cell migration and adhesion in metastatic squamous cell carcinoma of the head and neck by activating integrin αvβ3. Int J Mol Med. 2011;27(5):679–87.PubMed Li P, et al. Chemokine receptor 7 promotes cell migration and adhesion in metastatic squamous cell carcinoma of the head and neck by activating integrin αvβ3. Int J Mol Med. 2011;27(5):679–87.PubMed
29.
Zurück zum Zitat Janes SM, Watt FM. Switch from αvβ5 to αvβ6 integrin expression protects squamous cell carcinomas from anoikis. J Cell Biol. 2004;166:419–31.PubMedCrossRef Janes SM, Watt FM. Switch from αvβ5 to αvβ6 integrin expression protects squamous cell carcinomas from anoikis. J Cell Biol. 2004;166:419–31.PubMedCrossRef
Metadaten
Titel
Single-nucleotide polymorphisms of integrins are associated with the risk and lymph node metastasis of oral squamous cell carcinoma
verfasst von
Xiang-Rui Ma
Hui Cheng
Xiao-Yi Wang
Hao Liu
Dan Zhao
Publikationsdatum
01.12.2012
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 4/2012
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-012-0167-2

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