Expression of ADAMTS1 and Its Correlation with Angiogenesis in Primary Gastric Cancer and Lymph Node Metastasis
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ORIGINAL ARTICLE
Expression of ADAMTS1 and Its Correlation with Angiogenesis in Primary Gastric Cancer and Lymph Node Metastasis Jing Chen • Yu Zhi • Xiaojing Chang Shuanglong Zhang • Dongqiu Dai
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Received: 14 August 2011 / Accepted: 20 August 2012 / Published online: 22 September 2012 Ó Springer Science+Business Media, LLC 2012
Abstract Background A disintegrin and metallopeptidase with thrombospondin motif type 1 (ADAMTS1) is a recently discovered metalloproteinase with antiangiogenic activity. The function of ADAMTS1 in gastric cancer remains unknown. Therefore, we were interested in examining ADAMTS1 expression in human gastric cancer, as well as its possible correlation with angiogenesis. Methods The mRNA and protein expression of ADAMTS1, thrombospondin type I (TSP1), and vascular endothelial growth factor (VEGF) was evaluated by RT-PCR and immunohistochemistry, respectively, in 56 paired tumor and normal tissue samples, and corresponding metastatic lymph nodes (n = 42). Microvessel density (MVD) was also evaluated by immunohistochemistry. Results ADAMTS1 mRNA and protein levels were significantly lower in primary tumors than in corresponding normal tissues, and were significantly higher in metastatic lymph nodes compared to their matched primary tumors.
High ADAMTS1 mRNA and protein expression was found to be significantly associated with lymph node metastasis in primary tumors. There was a negative correlation between ADAMTS1 and VEGF mRNA and protein expression in primary gastric tumors and normal tissues. A negative correlation was also found between ADAMTS1 protein expression and MVD in primary gastric tumors. In contrast, no correlation was detected between ADAMTS1 and TSP1 mRNA and protein expression in primary gastric tumors, normal tissues, and metastatic lymph nodes. Conclusions These findings suggest that ADAMTS1 expression is altered in primary gastric cancer and paired lymph node metastasis. In addition, ADAMTS1 has angioinhibitory effects in primary gastric cancer due to its low expression and negative correlation with VEGF and MVD. However, it appears to lose its anti-angiogenic activity in metastatic lymph nodes in gastric cancer. Keywords ADAMTS1 TSP1 VEGF Gastric cancer Metastatic lymph node
Introduction J. Chen Y. Zhi X. Chang S. Zhang D. Dai (&) Department of Gastrointestinal Surgery, Fourth Affiliated Hospital, China Medical University, Chongshan East Road 4, Shenyang 110032, Liaoning, China e-mail: [email protected] J. Chen e-mail: [email protected] Y. Zhi e-mail: [email protected] X. Chang e-mail: [email protected] S. Zhang e-mail: [email protected]
Although there has been a decline in the incidence and mortality of gastric cancer in most countries over the last few decades, gastric cancer still remains the fourth most common type of cancer, and the second most common cause of cancer-related deaths worldwide. China alone accounts for 42 % of all gastric cancer cases [1]. Since surgical and medical treatments have not substantially improved survi
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