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Open Access 01-07-2012 | Research

The Role of SPARC Protein Expression in the Progress of Gastric Cancer

Authors: Lifeng Wang, Miling Yang, Lihui Shan, Lei Qi, Cuicui Chai, Qiufeng Zhou, Ke Yao, Hongmei Wu, Wenguang Sun

Published in: Pathology & Oncology Research | Issue 3/2012

Abstract

We aimed to investigate the expression of SPARC (secreted protein, acidic and rich in cysteine) in gastric cancer and its relationship with tumor angiogenesis and cancer cells proliferation. Protein expression of SPARC, VEGF, CD34 and Ki-67 in 80 cases of gastric cancer and 30 cases of normal gastric tissue was evaluated by immunohistochemistry. CD34 staining was used as an indicator of microvessel density (MVD). Ki-67 labeling Index (LI) indicated cancer cells proliferation. Statistical analysis was used to investigate its relationship with clinical characteristics, tumor angiogenesis and cancer cells proliferation. SPARC expression was mainly in the stromal cells surrounding the gastric cancer cells, and was statistically significant differences between gastric cancer and normal gastric tissue (P < 0.05). Both the expression of SPARC and VEGF were related to differentiation degree, clinical stage, Lauren classification and lymph node metastasis (P < 0.05). Expression of SPARC was significantly negatively correlated with the expression of VEGF and MVD in gastric cancer tissues. Expression of SPARC was also negatively correlated with Ki-67-LI. Our findings suggest that both the expression of SPARC and VEGF are closed to tumor angiogenesis in gastric cancer, SPARC inhibited tumor angiogenesis but VEGF promoted tumor angiogenesis. SPARC also inhibited cells proliferation of gastric cancer.

Zhan W, Han F (2008) Surgical therapy of gastric cancer in china. J Pract Oncol 23:91–93

Klagsbrun MD, Amore PA (1991) Regulators of angiogenesis. Annu Rev Physiol 53:217–239PubMedCrossRef

Dvorak HF, Brown LF, Detmer MD et al (1995) Vascualr permeability factor/vascular endothelial growth factor, microvascular hyperpermeability and angiogenesis. Am J Pathol 146:1029–1039PubMed

Raines EW, Lane TF, Iruela-Arispe ML et al (1992) The extracellular glycoprotein SPARC interacts with platelet-derived growth factor(PDGF)-AB and-BB and inbibits the binding of PDGF to its receptors. Proc Natl Acad Sci USA 89:1281–1285PubMedCrossRef

Ledda F, Bravo AI, Adris S et al (1997) The expression of the secreted protein acidic and rich in cysteine (SPARC) is associated with the neoplastic progression of human melanoma. J Invest Dermatol 108:210–214PubMedCrossRef

Hasselaar P, Sage EH (1992) SPARC antagonizes the effect of bFGF on the migration of bovine aortic endothelial cells. J Cell Biochem 49:272–283PubMedCrossRef

Zhao Z-S, Wang Yuan-Yu (2010) SPARC Is Associated with Gastric Cancer Progression and Poor Survival of Patients. Clin Cancer Res 16(1):260–268PubMedCrossRef

Volm M, Koomagi R, Mattern J et al (1997) Prognostic value of vascular endothelial growth factor and its receptor Flt-1 in squamous cell lung cancer. Int J Cancer 74(1):64–68PubMedCrossRef

Weidner N, Folkman J, Pozza F et al (1992) Tumor angiogenesis:a new significant independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst 84(9):1875–1887PubMed

10.

Ikeguchi M, Cai J, Yamane N et al (1999) Clinical significance of spontaneous apoptosis in advanced gastric adenocarcinoma [J]. Cancer 85(11):2329–2335PubMedCrossRef

11.

Ellen JE, Sage H (1996) Regulation of angiogenesis by SPARC and angiostatin: implications for tumor cell biology. Seminars in cancer biology 7:139–146CrossRef

12.

Yan Q, Sage EH (1999) SPARC, a matricellular glycoprotein with important biological functions. J Histochem Cytochem 47(12):1495–1505PubMedCrossRef

13.

Bradshaw AD, Sage EH (2001) SPARC, a matricellular protein that functions in cellular differentiation and tissue response to injury. J Clin Invest 107(9):1049–1054PubMedCrossRef

14.

Bornstein P, Sage EH (2002) Matricellular proteins: extracellular modulators of cell function. Curr Opin Cell Biol 14:608–616PubMedCrossRef

15.

Watkins G, Douglas-Jones A, Bryce R et al (2005) Increased levels of SPARC (osteonectin) in human breast cancer tissues and its association with clinical outcomes. Prostaglandins Leukot Essent Fatty Acids 72:267–272PubMedCrossRef

16.

Yamanaka M, Kanda K, Li NC et al (2001) Analysis of the gene expression of SPARC and its prognostic value for bladder cancer. J Urol 166:2495–2499PubMedCrossRef

17.

Koukourakis MI, Giatromanolaki A, Brekken RA et al (2003) Enhanced Expression of SPARC/Osteonectin in the Tumor associated Stroma of Non Small Cell Lung Cancer Is Correlated with Markers of Hypoxia/Acidity and with Poor Prognosis of Patients. Cancer Res 63:5376–5380PubMed

18.

Said N, Frierson JR, Chernauskas D et al (2009) The role of SPARC in the TRAMP model of prostate carcinogenesis and progression. Oncogene 28(39):3487–3498PubMedCrossRef

19.

Siina J, Arto K, Toru M et al (2010) Gene Expression Analysis Identifies Over-expression of CXCL1, SPARC, SPP1, and SULF1 in Gastric Cancer. Gene Chromosomes &Cancer 49(1):28–39CrossRef

20.

Alexandre C, LisaJG RP et al (2010) Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors. Molecular Cancer 9:138CrossRef

21.

Shanna AA, Lee BR, Andrew FM et al (2010) Lack of host SPARC enhances vascular function and tumor spread in an orthotopic murine model of pancreatic carcinoma. Disease Models & Mechanisms 3(1):57–72CrossRef

22.

Schultz C, Lemke N, Ge S et al (2002) Secreted protein acidic and rich in cysteine promotes glioma invasion and delays tumor growth in vivo [J]. Cancer Res 62(21):6270–6277PubMed

23.

Berse B, Brown LF, Van D (1992) Vascular permeability factor(vascular endothelial growth factor) gene is expressed differently in normal tissues, macrophages, and tumors. Mol Biol Cell 3:210–211

24.

Detmar M, Velasco P, Richard L et al (2000) Expression of vascular endothelial growth factor induces an invasive phenotype in human squamous cell carcinomas. Am J Pathol 156:159–167PubMedCrossRef

25.

Raspollini MR, Amunni G, Villanucci A et al (2004) Prognostic significance of microvessel density and vascular endothelial growth factor expression in advanced ovarian serous carcinoma [J]. Int J Gynecol Cancer 14(5):815–823PubMedCrossRef

26.

Bremnes RM, Camps C, Sirera R et al (2006) Angiogenesis in non-small cell lung cancer: the prognostic impact of neoangiogenesis and the cytokines VEGF and bFGF in tumours and blood. Lung Cancer 51(2):143–158PubMedCrossRef

27.

Yunker CK, Golembieski W, Lemke N et al (2008) SPARC-induced increase in glioma matrix and decrease in vascularity are associated with reduced VEGF expression and secretion. Int J Cancer 122:2735–2743PubMedCrossRef

28.

Chlenski A, Liu S, Crawford SE et al (2002) SPARC is a key Schwannian derived inhibitor controlling neuroblastoma tumor angiogenesis. Cancer Res 62:7357–7363PubMed

Title: The Role of SPARC Protein Expression in the Progress of Gastric Cancer
Authors: Lifeng Wang
Miling Yang
Lihui Shan
Lei Qi
Cuicui Chai
Qiufeng Zhou
Ke Yao
Hongmei Wu
Wenguang Sun
Publication date: 01-07-2012
Publisher: Springer Netherlands
Published in: Pathology & Oncology Research / Issue 3/2012
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI: https://doi.org/10.1007/s12253-012-9497-9

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