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Erschienen in: Clinical and Translational Oncology 7/2014

01.07.2014 | Research Article

Increased expression of α5β1-integrin is a prognostic marker for patients with gastric cancer

verfasst von: J. Ren, S. Xu, D. Guo, J. Zhang, S. Liu

Erschienen in: Clinical and Translational Oncology | Ausgabe 7/2014

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Abstract

Objective

The study was to evaluate the association of expression level of α5β1-integrin with clinicopathologic features and prognosis in gastric cancer (GC).

Methods

The expression of α5β1-integrin in normal gastric mucosa and GC tissue was detected with immunohistochemistry. The level of α5 and β1 mRNA in GC tissues and non-neoplastic tissues was evaluated in 48 paired cases by quantitative real-time polymerase chain reaction (qRT-PCR). Survival analysis by the Kaplan–Meier method was performed to assess prognostic significance.

Results

The α5β1-integrin expression was detected in 68.3 % (127/186) GC samples, and there was a significant difference on their positive expression rate between GC tissue and normal gastric mucosa (P < 0.001). The positive expression rate of α5β1-integrin in patients with poor histologic differentiation (P = 0.001), lymph node metastasis (P < 0.001), and recurrence (P < 0.001) group was heightened. Using Kaplan–Meier analysis, a comparison of survival curves of low versus high expresser of α5β1-integrin revealed a highly significant difference in human GC tissue (P = 0.002), which suggested that overexpression of α5β1-integrin is associated with a worse prognosis. Multivariate analyses showed that α5β1-integrin expression was independent risk factor predicting overall survival [Hazard ratio (HR) 1.594, 95 % confidence interval (CI) 1.236–2.408, P = 0.006] and disease-free survival [HR 3.952, 95 % CI 1.676–9.861, P = 0.003] in GC.

Conclusions

The α5β1-integrin promotes angiogenesis and associates with lymph node metastasis, vascular invasion and poor prognosis of GC. The current study shows that α5β1-integrin may be an independent prognostic factor for GC patients.
Literatur
1.
Zurück zum Zitat Price P, Sikore K. Stomach. In: Price P, Sikore K, editors. Treatment of Cancer, 4th ed. London: Arnold Press, 2002. pp. 583–99. Price P, Sikore K. Stomach. In: Price P, Sikore K, editors. Treatment of Cancer, 4th ed. London: Arnold Press, 2002. pp. 583–99.
2.
3.
Zurück zum Zitat Desgrosellier JS, Cheresh DA. Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer. 2010;10:9–22.PubMedCrossRef Desgrosellier JS, Cheresh DA. Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer. 2010;10:9–22.PubMedCrossRef
4.
Zurück zum Zitat Morozevich G, Kozlova N, Cheglakov I, Ushakova N, Berman A. Integrin α5β1 controls invasion of human breast carcinoma cells by direct and indirect modulation of MMP-2 collagenase activity. Cell Cycle. 2009;8(14):2219–25.PubMedCrossRef Morozevich G, Kozlova N, Cheglakov I, Ushakova N, Berman A. Integrin α5β1 controls invasion of human breast carcinoma cells by direct and indirect modulation of MMP-2 collagenase activity. Cell Cycle. 2009;8(14):2219–25.PubMedCrossRef
5.
Zurück zum Zitat Chi F, Fu D, Zhang X, Lv Z, Wang Z. Expression of the c-Met proto-oncogene and Integrin α5β1 in human gastric cardia adenocarcinoma. Biosci Biotechnol Biochem. 2012;76(8):1471–6.PubMedCrossRef Chi F, Fu D, Zhang X, Lv Z, Wang Z. Expression of the c-Met proto-oncogene and Integrin α5β1 in human gastric cardia adenocarcinoma. Biosci Biotechnol Biochem. 2012;76(8):1471–6.PubMedCrossRef
6.
Zurück zum Zitat Weston BS, Wahab NA, Mason RM. CTGF mediates TGF-beta-induced fibronectin matrix deposition by upregulating active alpha5beta1 integrin in human mesangial cells. J Am Soc Nephrol. 2003;14(3):601–10.PubMedCrossRef Weston BS, Wahab NA, Mason RM. CTGF mediates TGF-beta-induced fibronectin matrix deposition by upregulating active alpha5beta1 integrin in human mesangial cells. J Am Soc Nephrol. 2003;14(3):601–10.PubMedCrossRef
7.
Zurück zum Zitat Hynes RO. Cell-matrix adhesion in vascular development. J Thromb Haemost. 2007;5(S1):32–40.PubMedCrossRef Hynes RO. Cell-matrix adhesion in vascular development. J Thromb Haemost. 2007;5(S1):32–40.PubMedCrossRef
8.
Zurück zum Zitat Serini G, Valdembri D, Bussolino F. Integrins and angiogenesis: a sticky business. Exp Cell Res. 2006;312:651–8.PubMedCrossRef Serini G, Valdembri D, Bussolino F. Integrins and angiogenesis: a sticky business. Exp Cell Res. 2006;312:651–8.PubMedCrossRef
9.
Zurück zum Zitat Hood JD, Cheresh DA. Role of integrins in cell invasion and migration. Nat Rev Cancer. 2002;2(2):91–100.PubMedCrossRef Hood JD, Cheresh DA. Role of integrins in cell invasion and migration. Nat Rev Cancer. 2002;2(2):91–100.PubMedCrossRef
10.
Zurück zum Zitat Takenaka K, Shibuya M, Takeda Y, Hibino S, Gemma A, Ono Y, et al. Altered expression and function of beta1 integrins in a highly metastatic human lung adenocarcinoma cell line. Int J Oncol. 2000;17(6):1187–94.PubMed Takenaka K, Shibuya M, Takeda Y, Hibino S, Gemma A, Ono Y, et al. Altered expression and function of beta1 integrins in a highly metastatic human lung adenocarcinoma cell line. Int J Oncol. 2000;17(6):1187–94.PubMed
11.
Zurück zum Zitat Li LX, Welser-Alves J, van der Flier A, Boroujerdi A, Hynes RO, Milner R. An angiogenic role for the α5β1-integrin in promoting endothelial cell proliferation during cerebral hypoxia. Exp Neurol. 2012;237:46–54.PubMedCentralPubMedCrossRef Li LX, Welser-Alves J, van der Flier A, Boroujerdi A, Hynes RO, Milner R. An angiogenic role for the α5β1-integrin in promoting endothelial cell proliferation during cerebral hypoxia. Exp Neurol. 2012;237:46–54.PubMedCentralPubMedCrossRef
13.
Zurück zum Zitat Fidler IJ. Angiogenesis and cancer metastasis. Cancer J. 2000;2:S134–41. Fidler IJ. Angiogenesis and cancer metastasis. Cancer J. 2000;2:S134–41.
14.
Zurück zum Zitat Eliceiri BP, Cheresh DA. Adhesion events in angiogenesis. Curr Opin Cell Biol. 2001;13:563–8.PubMedCrossRef Eliceiri BP, Cheresh DA. Adhesion events in angiogenesis. Curr Opin Cell Biol. 2001;13:563–8.PubMedCrossRef
15.
Zurück zum Zitat Hynes RO. A reevaluation of integrins as regulators of angiogenesis. Nat Med. 2002;8(9):918–21.PubMedCrossRef Hynes RO. A reevaluation of integrins as regulators of angiogenesis. Nat Med. 2002;8(9):918–21.PubMedCrossRef
16.
Zurück zum Zitat Yang JT, Rayburn H, Hynes RO. Embryonic mesodermal defects in α5 integrin-deficient mice. Development. 1993;19:1093–105. Yang JT, Rayburn H, Hynes RO. Embryonic mesodermal defects in α5 integrin-deficient mice. Development. 1993;19:1093–105.
17.
Zurück zum Zitat Taverna D, Hynes RO. Reduced blood vessel formation and tumor growth in alpha5-integrin-negative teratocarcinomas and embryoid bodies. Cancer Res. 2001;61:5255–61.PubMed Taverna D, Hynes RO. Reduced blood vessel formation and tumor growth in alpha5-integrin-negative teratocarcinomas and embryoid bodies. Cancer Res. 2001;61:5255–61.PubMed
18.
Zurück zum Zitat Kesanakurti D, Chetty C, Dinh DH, Gujrati M, Rao JS. Role of MMP-2 in the regulation of IL-6/Stat3 survival signaling via interaction with a5β1 integrin in glioma. Oncogene. 2012. pp. 1–14. Kesanakurti D, Chetty C, Dinh DH, Gujrati M, Rao JS. Role of MMP-2 in the regulation of IL-6/Stat3 survival signaling via interaction with a5β1 integrin in glioma. Oncogene. 2012. pp. 1–14.
19.
Zurück zum Zitat Mitra A, Chakrabarti J, Chatterjee A. Binding of alpha5 monoclonal antibody to cell surface alpha5beta1 integrin modulates MMP-2 and MMP-7 activity in B16F10 melanoma cells. J Environ Pathol Toxicol Oncol. 2003;22:167–78.PubMedCrossRef Mitra A, Chakrabarti J, Chatterjee A. Binding of alpha5 monoclonal antibody to cell surface alpha5beta1 integrin modulates MMP-2 and MMP-7 activity in B16F10 melanoma cells. J Environ Pathol Toxicol Oncol. 2003;22:167–78.PubMedCrossRef
20.
Zurück zum Zitat Ogier C, Bernard A, Chollet AM, LE Diguardher T, Hanessian S, Charton G, et al. Matrix metalloproteinase-2 (MMP-2) regulates astrocyte motility in connection with the actin cytoskeleton and integrins. Glia. 2006;54:272–284. Ogier C, Bernard A, Chollet AM, LE Diguardher T, Hanessian S, Charton G, et al. Matrix metalloproteinase-2 (MMP-2) regulates astrocyte motility in connection with the actin cytoskeleton and integrins. Glia. 2006;54:272–284.
21.
Zurück zum Zitat Aplin AE, Howe A, Alahari SK, Juliano RL. Signal transduction and signal modulation by cell adhesion receptors: the role of integrins, cadherins, immunoglobulin-cell adhesion molecules, and selectins. Pharmacol Rev. 1998;50:197–263.PubMed Aplin AE, Howe A, Alahari SK, Juliano RL. Signal transduction and signal modulation by cell adhesion receptors: the role of integrins, cadherins, immunoglobulin-cell adhesion molecules, and selectins. Pharmacol Rev. 1998;50:197–263.PubMed
22.
Zurück zum Zitat Miyamoto S, Teramoto H, Gutkind JS, Yamada KM. Integrins can collaborate with growth factors for phosphorylation of receptor tyrosine kinases and MAP kinase activation: roles of integrin aggregation and occupancy of receptors. J Cell Biol. 1996;135:1633–42.PubMedCrossRef Miyamoto S, Teramoto H, Gutkind JS, Yamada KM. Integrins can collaborate with growth factors for phosphorylation of receptor tyrosine kinases and MAP kinase activation: roles of integrin aggregation and occupancy of receptors. J Cell Biol. 1996;135:1633–42.PubMedCrossRef
23.
Zurück zum Zitat Schwartz MA, Shattil SJ. Signaling networks linking integrins and rho family GTPases. Trends Biochem Sci. 2000;25:388–91.PubMedCrossRef Schwartz MA, Shattil SJ. Signaling networks linking integrins and rho family GTPases. Trends Biochem Sci. 2000;25:388–91.PubMedCrossRef
Metadaten
Titel
Increased expression of α5β1-integrin is a prognostic marker for patients with gastric cancer
verfasst von
J. Ren
S. Xu
D. Guo
J. Zhang
S. Liu
Publikationsdatum
01.07.2014
Verlag
Springer Milan
Erschienen in
Clinical and Translational Oncology / Ausgabe 7/2014
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-013-1133-y

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