Expression of MTA1 and VEGF-C in Esophageal Squamous Cell Carcinoma and Relationship between Them and Lymphangiogenesis_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

1. Department of Cardiovascular Surgery, Suining Central Hospital, Suining 629000 Sichuan, P. R. China;
2. Department of Cardiothoracic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000 Sichuan, P. R. China;
3. Department of Pathology, Central Hospital of Suining, Suining 629000 Sichuan, P. R. China;

Corresponding author：

Keywords：

Tumor metastasis associated genes-1 (MTA1); Vascular endothelial growth factor-C (VEGF-C); Esophageal squamous cell carcinoma; Lymphangiogenesis

DOI：

10.7507/1007-4848.20160063

Video：

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Objective To investigate the expression of tumor metastasis associated genes-1 (MTA1) and vascular endothelial growth factor-C (VEGF-C) in esophageal squamous cell carcinoma (ESCC) and the relationship between them and lymphangiogenesis. Method A total of 107 patients who received excision for ESCC in the Cardiothoracic Surgery Department of Suining Central Hospital from March 2013 through January 2014 were enrolled. And the paraffinembedded esophageal tissues in 56 healthy persons were collected. The expression of MTA1 and VEGF-C in ESCC was detected using the immunohistochemical method. And D2-40 was used to label the micro-lymphatic endothelial cells of the tumor tissues while the micro-lymphatic vessel density (LVD) was counted. Meanwhile, a statistical analysis was performed for the relationship between MTA1 with VEGF-C and clinical pathological parameters. Results The expression rates of MTA1 protein and VEGF-C protein in ESCC (50.4% and 58.8%, respectively) were higher than those in normal esophageal tissues with a statistical difference (P<0.05). Besides, their high expression rates in stage T₃/T₄ ESCC and lymph node metastasis group were significantly higher than those in stage T₁/T₂ ESCC and metastasisfree group, with statistical differences (P<0.05). The high expression rates of MTA1 and VEGF-C protein in ESCC with different TNM stages were compared using Kruskal-Wallis test with statistical differences (P<0.05). Moreover, a positive correlation existed in the expression level between MTA1 protein and VEGF-C protein of ESCC (Spearman coefficient r=0.512, P=0.000). And LVD of the high expression group for MTA1 protein and VEGF-C protein was statistically different from that of the low expression group (P<0.05). Conclusion The expression of MTA1 is positively correlated with the expression of VEGF-C in ESCC. And they may co-promote lymphangiogenesis and lymphatic metastasis in ESCC. Therefore, both can be used as the laboratory indicators to determine the prognosis of ESCC.

Citation： LIUJian-ping, FUMao-yong, XIAJuan, ZHANGYong-heng, GONGSheng, GUOYu-long. Expression of MTA1 and VEGF-C in Esophageal Squamous Cell Carcinoma and Relationship between Them and Lymphangiogenesis. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2016, 23(3): 268-273. doi: 10.7507/1007-4848.20160063 Copy

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2.	刘建平, 张永恒, 付茂勇. MTA1与肿瘤淋巴管血管生成. 医学综述, 2014, 20(6): 1040-1043.
3.	刘建平, 张永恒, 付茂勇. VEGF-C与食管鳞癌淋巴管生成的研究进展. 现代肿瘤医学, 2015, 23(9): 1315-1318.
4.	Hofer MD, Kuefer R, Varambally S, et al. The role of metastasis-associated protein 1 in prostate cancer progression. Cancer Res, 2004, 64: 825-829.
5.	Miyake K, Yoshizumi T, Imura S, et al. Expression of hypoxiain-ducible actor-1alpha, histone deacetylase 1, and metastasis-associated protein 1 in pancreatic carcinoma: correlation with poor prognosis with possible regulation. Pancreas, 2008, 36(3): e1-e9.
6.	袁杨, 肖波, 方强, 等. 食管癌脉管内瘤栓的研究进展. 中国胸心血管外科临床杂志, 2014, 21(5): 686-689.
7.	田东, 付茂勇. 肿瘤相关微淋巴管内皮细胞的研究进展. 肿瘤, 2011, 31(3): 280-284.
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9.	Nagaraj SR, Shilpa P, Rachaiah K, et al. Crosstalk between VEGF and MTA1 signaling pathway to aggressiveness of breast carcinoma. Mol Carcinog, 2015, 54(5): 333-350.
10.	Li SH, Tian H, Yue WM, et al. Overexpression of metastasis-asso-ciated protein 1 is significantly correlated with tumor angiogenesis and poor survival in patients with early-stage non-small cell lung cancer. Ann Surg Oncol, 2011, 18(7): 2048-2056.
11.	Kai L, Wang J, Ivanovic M, et al. Targeting prostate cancer angio-genesis through metastasis-associated protein 1(MTA1). Prostate, 2011, 71(3): 268-280.
12.	Prisco MG, Zannoni GF, De Stefano I, et al. Prognostic role of metastasis tumor antigen 1 in patients with ovarian cancer: a clinical study. Hum Pathol, 2012, 43(2): 282-288.
13.	Xie LX, Zhai TT, Yang LP, et al. Lymphangiogenesis and prognostic significance of vascular endothelial growth factor C in gastro-oesophageal junction adenocarcinoma. Int J Exp Pathol, 2013, 94(1): 39-46.
14.	Feng Y, Wang W, Hu J, et al. Expression of VEGF-C and VEGF-D as significant markers for assessment of lymphangiogenesis and lymph node metastasis in non-small cell lung cancer. Anat Rec (Hoboken), 2010, 293(5): 802-812.
15.	张泽进, 张东卫, 谭莹. 结肠癌VEGF-C表达与淋巴管生成、淋巴结转移的关系. 中华全科医学, 2013, 11(6): 867-869.
16.	Wakisaka N, Hirota K, Kondo S, et al. Induction of lymphangio-genesis through vascular endothelial growth factor-C/vascular endothelial growth factor receptor 3 axis and its correlation with lymph node metastasis in nasopharyngeal carcinoma. Oral Oncol, 2012, 48(8): 703-708.
17.	石小燕, 张亚东, 赵良平, 等. 早期宫颈癌组织中VEGF-C与COX-2的表达及相关性.华中科技大学学报(医学版), 2013, 42(3): 307-310.
18.	Ochi N, Matsuo Y, Sawai H, et al. Vascular endothelial growth factor-C secreted by pancreatic cancer cell line promotes lymphatic endothelial cell migration in an in vitro model of tumor lymphan-giogenesis. Pancreas, 2007, 34(4): 444-451.
19.	Wang CA, Harrell JC, Iwanaga R, et al. Vascular endothelial growth factor C promotes breast cancer progression via a novel antioxidant mechanism that involves regulation of superoxide dismutase 3. Breast Cancer Res, 2014, 16(5): 462.
20.	Peng J, Shao N, Peng H, et al. Prognostic significance of vascular endothelial growth factor expession in esophageal carcinoma: a meta-analysis. J BUON, 2013, 18(2): 398-406.
21.	Moon HE, Cheon H, Chun KH, et al. Metastasis-associated protein 1 enhances angiogenesis by stabilization of HIF-1. Oncol Rep, 2006, 16(4): 929-935.
22.	Du B, Yang ZY, Zhong XY, et al. Metastasis-associated protein 1 induces VEGF-C and facilitates lymphangiogenesis in colorectal cancer. World J Gastroenterol, 2011, 17(9): 1219-1226.
23.	Li DQ, Pakala SB, Nair SS, et al. Metastasis-associated protein 1/Nucleosome remodeling and histone deacetylase complex in cancer. Cancer Res, 2012, 72(2): 387-394.
24.	孙志刚, 谢家声. 食管鳞状细胞癌干细胞研究的现状及进展. 中国胸心血管外科临床杂志, 2013, 20(5): 583-587.
25.	Onogawa S, Kitadai Y, Tanaka S, et al. Regulation of vascular endothelial growth factor(VEGF)-C and VEGF-D expression by the organ microenvironment in human colon carcinoma. Eur J Cancer, 2004, 40(10)): 1604-1609.
26.	陈涛, 曾永鸿, 陈灿映, 等. 肿瘤发生发展过程中相关微环境的动态改变研究进展. 武汉大学学报(医学版), 2015, 36(2): 325-328.

1. 中国抗癌协会食管癌专业委员会. 食管癌规范化诊治指南(第一版). 北京: 中国协和医科大学出版社, 2011. 1-3.
2. 刘建平, 张永恒, 付茂勇. MTA1与肿瘤淋巴管血管生成. 医学综述, 2014, 20(6): 1040-1043.
3. 刘建平, 张永恒, 付茂勇. VEGF-C与食管鳞癌淋巴管生成的研究进展. 现代肿瘤医学, 2015, 23(9): 1315-1318.
4. Hofer MD, Kuefer R, Varambally S, et al. The role of metastasis-associated protein 1 in prostate cancer progression. Cancer Res, 2004, 64: 825-829.
5. Miyake K, Yoshizumi T, Imura S, et al. Expression of hypoxiain-ducible actor-1alpha, histone deacetylase 1, and metastasis-associated protein 1 in pancreatic carcinoma: correlation with poor prognosis with possible regulation. Pancreas, 2008, 36(3): e1-e9.
6. 袁杨, 肖波, 方强, 等. 食管癌脉管内瘤栓的研究进展. 中国胸心血管外科临床杂志, 2014, 21(5): 686-689.
7. 田东, 付茂勇. 肿瘤相关微淋巴管内皮细胞的研究进展. 肿瘤, 2011, 31(3): 280-284.
8. Deng X, Du L, Wang C, et al. Close association of metastasis-associated protein 1 overexpression with increased angiogenesis and poor survival in patients with histologically node-negative gastric cancer. World J Surg, 2013, 37(4): 792-798.
9. Nagaraj SR, Shilpa P, Rachaiah K, et al. Crosstalk between VEGF and MTA1 signaling pathway to aggressiveness of breast carcinoma. Mol Carcinog, 2015, 54(5): 333-350.
10. Li SH, Tian H, Yue WM, et al. Overexpression of metastasis-asso-ciated protein 1 is significantly correlated with tumor angiogenesis and poor survival in patients with early-stage non-small cell lung cancer. Ann Surg Oncol, 2011, 18(7): 2048-2056.
11. Kai L, Wang J, Ivanovic M, et al. Targeting prostate cancer angio-genesis through metastasis-associated protein 1(MTA1). Prostate, 2011, 71(3): 268-280.
12. Prisco MG, Zannoni GF, De Stefano I, et al. Prognostic role of metastasis tumor antigen 1 in patients with ovarian cancer: a clinical study. Hum Pathol, 2012, 43(2): 282-288.
13. Xie LX, Zhai TT, Yang LP, et al. Lymphangiogenesis and prognostic significance of vascular endothelial growth factor C in gastro-oesophageal junction adenocarcinoma. Int J Exp Pathol, 2013, 94(1): 39-46.
14. Feng Y, Wang W, Hu J, et al. Expression of VEGF-C and VEGF-D as significant markers for assessment of lymphangiogenesis and lymph node metastasis in non-small cell lung cancer. Anat Rec (Hoboken), 2010, 293(5): 802-812.
15. 张泽进, 张东卫, 谭莹. 结肠癌VEGF-C表达与淋巴管生成、淋巴结转移的关系. 中华全科医学, 2013, 11(6): 867-869.
16. Wakisaka N, Hirota K, Kondo S, et al. Induction of lymphangio-genesis through vascular endothelial growth factor-C/vascular endothelial growth factor receptor 3 axis and its correlation with lymph node metastasis in nasopharyngeal carcinoma. Oral Oncol, 2012, 48(8): 703-708.
17. 石小燕, 张亚东, 赵良平, 等. 早期宫颈癌组织中VEGF-C与COX-2的表达及相关性.华中科技大学学报(医学版), 2013, 42(3): 307-310.
18. Ochi N, Matsuo Y, Sawai H, et al. Vascular endothelial growth factor-C secreted by pancreatic cancer cell line promotes lymphatic endothelial cell migration in an in vitro model of tumor lymphan-giogenesis. Pancreas, 2007, 34(4): 444-451.
19. Wang CA, Harrell JC, Iwanaga R, et al. Vascular endothelial growth factor C promotes breast cancer progression via a novel antioxidant mechanism that involves regulation of superoxide dismutase 3. Breast Cancer Res, 2014, 16(5): 462.
20. Peng J, Shao N, Peng H, et al. Prognostic significance of vascular endothelial growth factor expession in esophageal carcinoma: a meta-analysis. J BUON, 2013, 18(2): 398-406.
21. Moon HE, Cheon H, Chun KH, et al. Metastasis-associated protein 1 enhances angiogenesis by stabilization of HIF-1. Oncol Rep, 2006, 16(4): 929-935.
22. Du B, Yang ZY, Zhong XY, et al. Metastasis-associated protein 1 induces VEGF-C and facilitates lymphangiogenesis in colorectal cancer. World J Gastroenterol, 2011, 17(9): 1219-1226.
23. Li DQ, Pakala SB, Nair SS, et al. Metastasis-associated protein 1/Nucleosome remodeling and histone deacetylase complex in cancer. Cancer Res, 2012, 72(2): 387-394.
24. 孙志刚, 谢家声. 食管鳞状细胞癌干细胞研究的现状及进展. 中国胸心血管外科临床杂志, 2013, 20(5): 583-587.
25. Onogawa S, Kitadai Y, Tanaka S, et al. Regulation of vascular endothelial growth factor(VEGF)-C and VEGF-D expression by the organ microenvironment in human colon carcinoma. Eur J Cancer, 2004, 40(10)): 1604-1609.
26. 陈涛, 曾永鸿, 陈灿映, 等. 肿瘤发生发展过程中相关微环境的动态改变研究进展. 武汉大学学报(医学版), 2015, 36(2): 325-328.

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Expression of MTA1 and VEGF-C in Esophageal Squamous Cell Carcinoma and Relationship between Them and Lymphangiogenesis

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