Relationships Between Expressions of Somatostatin Receptor Subtypes and Angiogenesis in Colorectal Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

QIU Chengzhi ¹ , HUANG Zhongxin ² , WU Youyi ¹ , QIU Jianlong. ²

1.Department of General Surgery, The Affiliated Second Hospital, Fujian Medical University, Quanzhou 362000, Fujian Province, China;;
2.Department of Pathology, The Affiliated Second Hospital, Fujian Medical University, Quanzhou 362000, Fujian Province, China;

Corresponding author：

Keywords：

Somatostatin receptor subtype; Colorectal cancer; Angiogenesis; Immunohistochemistry

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Objective To study the relationships between expressions of somatostatin receptor subtypes（SSTR1-SSTR5） and angiogenesis in colorectal cancer. Methods The expressions of SSTR1-SSTR5, VEGF, and CD34 in the paraffin sections of colorectal cancer tissues from 127 cases were detected by the standard streptavidin-peroxidase (SP) technique. CD34 was used as a marker to account microvessel density (MVD) in colorectal cancer tissues. The relationships between the expressions of SSTR1-SSTR5 and VEGF expression, or MVD were analyzed. Results The positive expression rate of SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5 was 64.6% （82/127）, 36.2% （46/127）, 18.9% （24/127）, 18.9% （24/127）, and 38.6% （49/127） in colorectal cancer tissues, meanwhile, the positive expression rate of VEGF was 63.8% （81/127） and MVD was (34.67±16.62)/HP in colorectal cancer tissues. The positive expression rate of VEGF (47.8%， 22/46) and MVD 〔(29.00±15.32)/HP〕 in colorectal cancer tissues with SSTR2 positive expression were significantly lower than those in colorectal cancer tissues with SSTR2 negative expression 〔72.8%， 59/81； (37.90±16.56)/HP〕, P lt;0.05. There were no relationships between SSTR1, SSTR3, SSTR4, and SSTR5 expression and VEGF expression or MVD （P gt;0.05）. Conclusion The positive expression of SSTR2 is related with angiogenesis in colorectal cancer tissues.

Citation： QIU Chengzhi,HUANG Zhongxin,WU Youyi,QIU Jianlong.. Relationships Between Expressions of Somatostatin Receptor Subtypes and Angiogenesis in Colorectal Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(11): 1164-1167. doi: Copy

1.	Bhandari S, Watson N, Long E, et al. Expression of somatostatin and somatostatin receptor subtypes 1-5 in human normal and diseased kidney [J]. J Histochem Cytochem, 2008; 56(8): 733-743.
2.	Taboada GF, Luque RM, Neto LV, et al. Quantitative analysis of somatostatin receptor subtypes (1-5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR [J]. Eur J Endocrinol, 2008; 158(3): 295-303.
3.	Righi L, Volante M, Tavaglione V, et al. Somatostatin receptor tissue distribution in lung neuroendocrine tumours: a clinicopathologic and immunohistochemical study of 218 ‘clinically aggressive’ cases [J]. Ann Oncol, 2010; 21(3): 548-555.
4.	邱成志, 王川, 黄种心, 等. 结直肠癌组织中生长抑素受体亚型表达与Ki-67、bcl-2、p53的关系 [J]. 中华实验外科杂志, 2006; 23(9): 1101-1102.
5.	Grozinsky-Glasberg S, Shimon I, Korbonits M, et al. Somatostatin analogues in the control of neuroendocrine tumours: efficacy and mechanisms [J]. Endocr Relat Cancer, 2008; 15(3): 701-720.
6.	Dal Monte M, Cammalleri M, Martini D, et al. Antiangiogenic role of somatostatin receptor 2 in a model of hypoxia-induced neovascularization in the retina: results from transgenic mice [J]. Invest Ophthalmol Vis Sci, 2007; 48(8): 3480-3489.
7.	郁宝铭. 结肠肿瘤 [A]. 见: 吴阶平，裘法祖. 黄家驷外科学 [M]. 第6版. 北京: 人民卫生出版社, 2000: 1135-1136.
8.	魏学明, 顾国利, 任力, 等. 胃癌组织中EGFR、C-erbB-2、VEGF及COX-2的表达及意义 [J]. 中国普外基础与临床杂志, 2009; 16(11): 900-905.
9.	梁忆波, 崔琳, 于建宪, 等. 组织芯片检测结直肠癌中HGF/c-met的表达及其与肿瘤血管生成的关系 [J]. 中国普外基础与临床杂志, 2010; 17(7): 713-718.
10.	Cook KM, Figg WD. Angiogenesis inhibitors: current strategies and future prospects [J]. CA Cancer J Clin, 2010; 60(4): 222-243.
11.	Nyberg P, Xie L, Kalluri R. Endogenous inhibitors of angiogenesis [J]. Cancer Res, 2005; 65(10): 3967-3979.
12.	Mori T, Sasaki J, Aoyama Y, et al. Modulation of endogenous VEGF-A expression under hypoxia by using artificial transcription factors [J]. Nucleic Acids Symp Ser (Oxf), 2008; (52): 187-188.
13.	Matei D, Kelich S, Cao L, et al. PDGF BB induces VEGF secretion in ovarian cancer [J]. Cancer Biol Ther, 2007; 6(12): 1951-1959.
14.	Park HJ, Kim MN, Kim JG, et al. Up-regulation of VEGF expression by NGF that enhances reparative angiogenesis during thymic regeneration in adult rat [J]. Biochim Biophys Acta, 2007; 1773(9): 1462-1472.
15.	Bian ZM, Elner SG, Elner VM. Regulation of VEGF mRNA expression and protein secretion by TGF-beta2 in human retinal pigment epithelial cells [J]. Exp Eye Res, 2007; 84(5): 812-822.
16.	Hollborn M, Stathopoulos C, Steffen A, et al. Positive feedback regulation between MMP-9 and VEGF in human RPE cells [J]. Invest Ophthalmol Vis Sci, 2007; 48(9): 4360-4367.
17.	Ho C, Hsu YC, Tseng CC, et al. Simvastatin alleviates diabetes-induced VEGF-mediated nephropathy via the modulation of Ras signaling pathway [J]. Ren Fail, 2008; 30(5): 557-565.
18.	Li L, Zhang R, Fang ZY, et al. Suppression of vascular endothelial growth factor (VEGF) expression by targeting the Bcr-Abl oncogene and protein tyrosine kinase activity in Bcr-Abl-positive leukaemia cells [J]. J Int Med Res, 2009; 37(2): 426-437.
19.	Kanai M, Wei D, Li Q, et al. Loss of Krüppel-like factor 4 expression contributes to Sp1 overexpression and human gastric cancer development and progression [J]. Clin Cancer Res, 2006; 12(21): 6395-6402.
20.	Montero E, Abreu C, Tonino P. Relationship between VEGF and p53 expression and tumor cell proliferation in human gastrointestinal carcinomas [J]. J Cancer Res Clin Oncol, 2008; 134(2): 193-201.
21.	Zhang J, Lu A, Li L, et al. p16 Modulates VEGF expression via its interaction with HIF-1α in breast cancer cells [J]. Cancer Invest, 2010; 28(6): 588-597.
22.	Tian T, Nan KJ, Wang SH, et al. PTEN regulates angiogenesis and VEGF expression through phosphatase-dependent and -independent mechanisms in HepG2 cells [J]. Carcinogenesis, 2010; 31(7): 1211-1219.
23.	温德才, 耿建利, 高若辉, 等. 内皮抑素、bFGF及CD34在胆囊癌中的表达及其意义 [J]. 中国普外基础与临床杂志, 2009; 16(6): 470-474.
24.	Arena S, Pattarozzi A, Corsaro A, et al. Somatostatin receptor subtype-dependent regulation of nitric oxide release: involvement of different intracellular pathways [J]. Mol Endocrinol, 2005; 19(1): 255-267.
25.	Kumar M, Liu ZR, Thapa L, et al. Anti-angiogenic effects of somatostatin receptor subtype 2 on human pancreatic cancer xenografts [J]. Carcinogenesis, 2004; 25(11): 2075-2081.
26.	Liu AM, Wong YH. Activation of nuclear factor κB by somatostatin type 2 receptor in pancreatic acinar AR42J cells involves Gα14 and multiple signaling components: a mechanism requiring protein kinase C, calmodulin-dependent kinase Ⅱ, ERK, and c-Src [J]. J Biol Chem, 2005; 280(41): 34617-34625.
27.	Ben-Shlomo A, Pichurin O, Barshop NJ, et al. Selective regulation of somatostatin receptor subtype signaling: evidence for constitutive receptor activation [J]. Mol Endocrinol, 2007; 21(10): 2565-2578.
28.	O’Toole D, Saveanu A, Couvelard A, et al. The analysis of quantitative expression of somatostatin and dopamine receptors in gastro-entero-pancreatic tumours opens new therapeutic strategies [J]. Eur J Endocrinol, 2006; 155(6): 849-857.

1. Bhandari S, Watson N, Long E, et al. Expression of somatostatin and somatostatin receptor subtypes 1-5 in human normal and diseased kidney [J]. J Histochem Cytochem, 2008; 56(8): 733-743.
2. Taboada GF, Luque RM, Neto LV, et al. Quantitative analysis of somatostatin receptor subtypes (1-5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR [J]. Eur J Endocrinol, 2008; 158(3): 295-303.
3. Righi L, Volante M, Tavaglione V, et al. Somatostatin receptor tissue distribution in lung neuroendocrine tumours: a clinicopathologic and immunohistochemical study of 218 ‘clinically aggressive’ cases [J]. Ann Oncol, 2010; 21(3): 548-555.
4. 邱成志, 王川, 黄种心, 等. 结直肠癌组织中生长抑素受体亚型表达与Ki-67、bcl-2、p53的关系 [J]. 中华实验外科杂志, 2006; 23(9): 1101-1102.
5. Grozinsky-Glasberg S, Shimon I, Korbonits M, et al. Somatostatin analogues in the control of neuroendocrine tumours: efficacy and mechanisms [J]. Endocr Relat Cancer, 2008; 15(3): 701-720.
6. Dal Monte M, Cammalleri M, Martini D, et al. Antiangiogenic role of somatostatin receptor 2 in a model of hypoxia-induced neovascularization in the retina: results from transgenic mice [J]. Invest Ophthalmol Vis Sci, 2007; 48(8): 3480-3489.
7. 郁宝铭. 结肠肿瘤 [A]. 见: 吴阶平，裘法祖. 黄家驷外科学 [M]. 第6版. 北京: 人民卫生出版社, 2000: 1135-1136.
8. 魏学明, 顾国利, 任力, 等. 胃癌组织中EGFR、C-erbB-2、VEGF及COX-2的表达及意义 [J]. 中国普外基础与临床杂志, 2009; 16(11): 900-905.
9. 梁忆波, 崔琳, 于建宪, 等. 组织芯片检测结直肠癌中HGF/c-met的表达及其与肿瘤血管生成的关系 [J]. 中国普外基础与临床杂志, 2010; 17(7): 713-718.
10. Cook KM, Figg WD. Angiogenesis inhibitors: current strategies and future prospects [J]. CA Cancer J Clin, 2010; 60(4): 222-243.
11. Nyberg P, Xie L, Kalluri R. Endogenous inhibitors of angiogenesis [J]. Cancer Res, 2005; 65(10): 3967-3979.
12. Mori T, Sasaki J, Aoyama Y, et al. Modulation of endogenous VEGF-A expression under hypoxia by using artificial transcription factors [J]. Nucleic Acids Symp Ser (Oxf), 2008; (52): 187-188.
13. Matei D, Kelich S, Cao L, et al. PDGF BB induces VEGF secretion in ovarian cancer [J]. Cancer Biol Ther, 2007; 6(12): 1951-1959.
14. Park HJ, Kim MN, Kim JG, et al. Up-regulation of VEGF expression by NGF that enhances reparative angiogenesis during thymic regeneration in adult rat [J]. Biochim Biophys Acta, 2007; 1773(9): 1462-1472.
15. Bian ZM, Elner SG, Elner VM. Regulation of VEGF mRNA expression and protein secretion by TGF-beta2 in human retinal pigment epithelial cells [J]. Exp Eye Res, 2007; 84(5): 812-822.
16. Hollborn M, Stathopoulos C, Steffen A, et al. Positive feedback regulation between MMP-9 and VEGF in human RPE cells [J]. Invest Ophthalmol Vis Sci, 2007; 48(9): 4360-4367.
17. Ho C, Hsu YC, Tseng CC, et al. Simvastatin alleviates diabetes-induced VEGF-mediated nephropathy via the modulation of Ras signaling pathway [J]. Ren Fail, 2008; 30(5): 557-565.
18. Li L, Zhang R, Fang ZY, et al. Suppression of vascular endothelial growth factor (VEGF) expression by targeting the Bcr-Abl oncogene and protein tyrosine kinase activity in Bcr-Abl-positive leukaemia cells [J]. J Int Med Res, 2009; 37(2): 426-437.
19. Kanai M, Wei D, Li Q, et al. Loss of Krüppel-like factor 4 expression contributes to Sp1 overexpression and human gastric cancer development and progression [J]. Clin Cancer Res, 2006; 12(21): 6395-6402.
20. Montero E, Abreu C, Tonino P. Relationship between VEGF and p53 expression and tumor cell proliferation in human gastrointestinal carcinomas [J]. J Cancer Res Clin Oncol, 2008; 134(2): 193-201.
21. Zhang J, Lu A, Li L, et al. p16 Modulates VEGF expression via its interaction with HIF-1α in breast cancer cells [J]. Cancer Invest, 2010; 28(6): 588-597.
22. Tian T, Nan KJ, Wang SH, et al. PTEN regulates angiogenesis and VEGF expression through phosphatase-dependent and -independent mechanisms in HepG2 cells [J]. Carcinogenesis, 2010; 31(7): 1211-1219.
23. 温德才, 耿建利, 高若辉, 等. 内皮抑素、bFGF及CD34在胆囊癌中的表达及其意义 [J]. 中国普外基础与临床杂志, 2009; 16(6): 470-474.
24. Arena S, Pattarozzi A, Corsaro A, et al. Somatostatin receptor subtype-dependent regulation of nitric oxide release: involvement of different intracellular pathways [J]. Mol Endocrinol, 2005; 19(1): 255-267.
25. Kumar M, Liu ZR, Thapa L, et al. Anti-angiogenic effects of somatostatin receptor subtype 2 on human pancreatic cancer xenografts [J]. Carcinogenesis, 2004; 25(11): 2075-2081.
26. Liu AM, Wong YH. Activation of nuclear factor κB by somatostatin type 2 receptor in pancreatic acinar AR42J cells involves Gα14 and multiple signaling components: a mechanism requiring protein kinase C, calmodulin-dependent kinase Ⅱ, ERK, and c-Src [J]. J Biol Chem, 2005; 280(41): 34617-34625.
27. Ben-Shlomo A, Pichurin O, Barshop NJ, et al. Selective regulation of somatostatin receptor subtype signaling: evidence for constitutive receptor activation [J]. Mol Endocrinol, 2007; 21(10): 2565-2578.
28. O’Toole D, Saveanu A, Couvelard A, et al. The analysis of quantitative expression of somatostatin and dopamine receptors in gastro-entero-pancreatic tumours opens new therapeutic strategies [J]. Eur J Endocrinol, 2006; 155(6): 849-857.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Relationships Between Expressions of Somatostatin Receptor Subtypes and Angiogenesis in Colorectal Cancer

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