Inhibitory effect of stomatin-like protein 2 (SLP-2) on growth of transplanted tumor of esophageal squamous cell carcinoma in nude mice_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

SONG Shuai ¹ , TIAN Di ² , CUI Yong ¹ , GAO Zhi ¹ , WANG Tianyou ¹ , HU Jian ¹ ,  CHANG Dong ¹

1. Department of Thoracic Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, P.R.China;
2. Department of Infectious Diseases, China Meitan General Hospital, Beijing, 100028, P.R.China;

Corresponding author：

CHANG Dong, Email: dchang2005@163.com

Keywords：

Stomatin-like protein 2; esophageal squamous cell carcinoma; orthotopic implantation animal model; in vivo imaging

DOI：

10.7507/1007-4848.201709036

Video：

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Objective To observe the growth of orthotopic transplanted tumor in nude mice after stomatin-like protein 2 (SLP-2) expression decreased, and to further study the role of SLP-2 in the development and progression of esophageal squamous cell carcinoma. Methods Using RNA interference technique, esophageal squamous cell carcinoma cell lines with specific expression of SLP-2 and stable expression of luciferase were established. The healthy female nude mice with weight ranging from 19 to 22 g were randomly divided into 3 groups (n=12), 6 mice were used to establish subcutaneous xenografts, and the other 6 mice were used to establish the orthotopic transplanted tumor model (Group 1: cell infected with SLP-2-1 plasmid; group 2: cell infected with SLP-2-2 plasmid; group 3: cell infected with SHGFP plasmid). Index of the experiment end was weight loss and poor general situation in any mouse. Before the nude mice were sacrificed, the luciferase value of the tumor was detected by using in vivo imaging technique. After the nude mice were sacrificed, the primary tumor was removed for pathology examination. Results There was no significant difference in region of interest (ROI) value between the group 1 and group 2 (P=0.943). The ROI value for both groups 1 and 2 was significantly lower than that in the group 3 (P=0.002, P=0.000). The primary tumor infiltrated into the muscularis propria of esophageal was observed in all groups. Conclusion SLP-2 is involved in the development and progression of esophageal squamous cell carcinoma, and the decrease of SLP-2 expression can inhibit the growth of esophageal squamous cell carcinoma.

Citation： SONG Shuai, TIAN Di, CUI Yong, GAO Zhi, WANG Tianyou, HU Jian, CHANG Dong. Inhibitory effect of stomatin-like protein 2 (SLP-2) on growth of transplanted tumor of esophageal squamous cell carcinoma in nude mice. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2018, 25(10): 885-889. doi: 10.7507/1007-4848.201709036 Copy

1.	Wang Y, Morrow JS. Identification and characterization of human SLP-2, a novel homologue of stomatin (band 7.2b) present in erythrocytes and other tissues. J Biol Chem, 2000, 275(11): 8062-8071.
2.	Da Cruz S, De Marchi U, Frieden M, et al. SLP-2 negatively modulates mitochondrial sodium-calcium exchange. Cell Calcium, 2010, 47(1): 11-18.
3.	张立勇, 丁芳, 刘仲敏, 等. SLP-2 基因反义核酸对食管鳞癌细胞系 TE12 生长和增殖的影响. 癌症, 2005, 24(2): 155-159.
4.	冯旺琴, 崔竹梅, 冯凤芝, 等. SLP-2 mRNA 在子宫内膜癌中的表达及其意义. 中华妇产科杂志, 2005, 40(8): 553-557.
5.	Cao WF, Zhang LY, Liu MB, et al. Prognostic significance of stomatin-like protein 2 overexpression in laryngeal squamous cell carcinoma: clinical, histologic, and immunohistochemistry analyses with tissue microarray. Hum Pathol, 2007, 38(5): 747-752.
6.	Chang D, Ma K, Gong M, et al. SLP-2 overexpression is associated with tumour distant metastasis and poor prognosis in pulmonary squamous cell carcinoma. Biomarkers, 2010, 15(2): 104-110.
7.	Luo A, Kong J, Hu G, et al. Discovery of Ca2+-relevant and differentiation-associated genes downregulated in esophageal squamous cell carcinoma using cDNA microarray. Oncogene, 2004, 23(6): 1291-1299.
8.	Cao W, Zhang B, Ding F, et al. Expression of SLP-2 was associated with invasion of esophageal squamous cell carcinoma. PLoS One, 2013, 8(5): e63890.
9.	Song S, Chang D, Cui Y, et al. New orthotopic implantation model of human esophageal squamous cell carcinoma in athymic nude mice. Thorac Cancer, 2014, 5(5): 417-424.
10.	Sun F, Ding W, He JH, et al. Stomatin-like protein 2 is overexpressed in epithelial ovarian cancer and predicts poor patient survival. BMC Cancer, 2015, 15: 746.
11.	Xiao B, Xie Z, Guo L, et al. Stomatin-like protein 2 expression is associated with clinical survival in patients with cervical cancer. Int J Clin Exp Pathol, 2015, 8(2): 1804-1809.
12.	Bartolome A, Boskovic S, Paunovic I, et al. Stomatin-like protein 2 overexpression in papillary thyroid carcinoma is significantly associated with high-risk clinicopathological parameters and BRAFV600E mutation. APMIS, 2016, 124(4): 271-277.
13.	Li XH, He F, Yan SM, et al. Increased expression of stomatin-like protein 2 (STOML2) predicts decreased survival in gastric adenocarcinoma: a retrospective study. Med Oncol, 2014, 31(1): 763.
14.	Zhang L, Ding F, Cao W, et al. Stomatin-like protein 2 is overexpressed in cancer and involved in regulating cell growth and cell adhesion in human esophageal squamous cell carcinoma. Clin Cancer Res, 2006, 12(5): 1639-1646.
15.	曹文枫, 张立勇, 张斌, 等. SLP-2 蛋白在食管鳞状细胞癌中的表达及其与肿瘤侵袭转移的关系. 中华肿瘤杂志, 2010, 32(11): 830-833.
16.	Wang Y, Cao W, Yu Z, et al. Downregulation of a mitochondria associated protein SLP-2 inhibits tumor cell motility, proliferation and enhances cell sensitivity to chemotherapeutic reagents. Cancer Biol Ther, 2009, 8(17): 1651-1658.

1. Wang Y, Morrow JS. Identification and characterization of human SLP-2, a novel homologue of stomatin (band 7.2b) present in erythrocytes and other tissues. J Biol Chem, 2000, 275(11): 8062-8071.
2. Da Cruz S, De Marchi U, Frieden M, et al. SLP-2 negatively modulates mitochondrial sodium-calcium exchange. Cell Calcium, 2010, 47(1): 11-18.
3. 张立勇, 丁芳, 刘仲敏, 等. SLP-2 基因反义核酸对食管鳞癌细胞系 TE12 生长和增殖的影响. 癌症, 2005, 24(2): 155-159.
4. 冯旺琴, 崔竹梅, 冯凤芝, 等. SLP-2 mRNA 在子宫内膜癌中的表达及其意义. 中华妇产科杂志, 2005, 40(8): 553-557.
5. Cao WF, Zhang LY, Liu MB, et al. Prognostic significance of stomatin-like protein 2 overexpression in laryngeal squamous cell carcinoma: clinical, histologic, and immunohistochemistry analyses with tissue microarray. Hum Pathol, 2007, 38(5): 747-752.
6. Chang D, Ma K, Gong M, et al. SLP-2 overexpression is associated with tumour distant metastasis and poor prognosis in pulmonary squamous cell carcinoma. Biomarkers, 2010, 15(2): 104-110.
7. Luo A, Kong J, Hu G, et al. Discovery of Ca2+-relevant and differentiation-associated genes downregulated in esophageal squamous cell carcinoma using cDNA microarray. Oncogene, 2004, 23(6): 1291-1299.
8. Cao W, Zhang B, Ding F, et al. Expression of SLP-2 was associated with invasion of esophageal squamous cell carcinoma. PLoS One, 2013, 8(5): e63890.
9. Song S, Chang D, Cui Y, et al. New orthotopic implantation model of human esophageal squamous cell carcinoma in athymic nude mice. Thorac Cancer, 2014, 5(5): 417-424.
10. Sun F, Ding W, He JH, et al. Stomatin-like protein 2 is overexpressed in epithelial ovarian cancer and predicts poor patient survival. BMC Cancer, 2015, 15: 746.
11. Xiao B, Xie Z, Guo L, et al. Stomatin-like protein 2 expression is associated with clinical survival in patients with cervical cancer. Int J Clin Exp Pathol, 2015, 8(2): 1804-1809.
12. Bartolome A, Boskovic S, Paunovic I, et al. Stomatin-like protein 2 overexpression in papillary thyroid carcinoma is significantly associated with high-risk clinicopathological parameters and BRAFV600E mutation. APMIS, 2016, 124(4): 271-277.
13. Li XH, He F, Yan SM, et al. Increased expression of stomatin-like protein 2 (STOML2) predicts decreased survival in gastric adenocarcinoma: a retrospective study. Med Oncol, 2014, 31(1): 763.
14. Zhang L, Ding F, Cao W, et al. Stomatin-like protein 2 is overexpressed in cancer and involved in regulating cell growth and cell adhesion in human esophageal squamous cell carcinoma. Clin Cancer Res, 2006, 12(5): 1639-1646.
15. 曹文枫, 张立勇, 张斌, 等. SLP-2 蛋白在食管鳞状细胞癌中的表达及其与肿瘤侵袭转移的关系. 中华肿瘤杂志, 2010, 32(11): 830-833.
16. Wang Y, Cao W, Yu Z, et al. Downregulation of a mitochondria associated protein SLP-2 inhibits tumor cell motility, proliferation and enhances cell sensitivity to chemotherapeutic reagents. Cancer Biol Ther, 2009, 8(17): 1651-1658.

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Inhibitory effect of stomatin-like protein 2 (SLP-2) on growth of transplanted tumor of esophageal squamous cell carcinoma in nude mice

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