The relationship between stromal cell derived SPARC in human gastric cancer tissue and its clinicopathologic significance
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Yi Gao1,*, Shui-Ping Yin2,*, Xu-Shi Xie3, Dan-Dan Xu4 and Wei-Dong Du1
1Department of Pathology, Anhui Medical University, Hefei 230032, People's Republic of China
2Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, People's Republic of China
3Department of Biology, School of Life Sciences, Anhui Medical University, Hefei 230032, People's Republic of China
4Department of Infectious Diseases, The Fourth Affiliated Hospital of Anhui Medical University, Hefei 230000, People's Republic of China
*These authors have contributed equally to this work
Wei-Dong Du, email: [email protected]
Keywords: SPARC, cancer-associated fibroblasts, tumor-associated macrophages, gastric cancer, tumor stroma
Received: October 24, 2016 Accepted: August 26, 2017 Published: September 21, 2017
Background: We aimed to investigate the cellular source of secreted protein acidic and rich in cysteine (SPARC) in gastric cancer tissues and the relationship between SPARC expression and its prognostic significance.
Methods: The expression of SPARC in 365 primary advanced gastric adenocarcinomas and 39 non-cancerous tissues was evaluated by immunohistochemical staining. Double-immunofluorescence staining was used to reveal the cellular source of SPARC in tumor tissues. Western blotting and immunofluorescence staining were applied for verifying the endogenous expression of SPARC in human cell lines of gastric cancer and fibroblast.
Results: Higher positivity of SPARC was observed in gastric cancer tissues than non-cancerous gastric tissues (P=0.000). The positivity of SPARC was related to age (P=0.032), tumor location (P=0.018), depth of tumor invasion (P=0.011), nodal metastasis (P=0.023), TNM stage (P=0.034), the differentiation degree (P=0.006) and pathological type (P=0.002) of gastric cancer. SPARC in gastric cancer tissues was mainly expressed by cancer-associated fibroblasts. SPARC also appeared in neovascular endothelial cells and a few tumor-associated macrophages. The endogenous expression of SPARC in fibroblasts was suppressed by mucus-producing gastric adenocarcinoma cells(MKN-45). Increased SPARC expression in gastric cancer tissue was suggestive of a shorter cumulative survival in the patients with gastric adenocarcinoma, though this difference was not statistically significant(P>0.05).
Conclusion: SPARC in human gastric cancer tissue was derived from the stromal cells and was mainly produced by cancer-associated fibroblasts. Production of SPARC in fibroblasts was reduced by the mucus-producing gastric adenocarcinoma cells.
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