Expressions and Clinical Significance of Chemokines Factor Receptors 4 and Chemokines Factor Receptors 7 in Gastric Cancer Tissues_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 YANGJing ,  HUANGXian-bin , HAOXiang-yong , WEILi , JINGWu-tang ,  GUOTian-kang

The First Department of General Surgery, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China;

Corresponding?author：

GUOTian-kang, Email: guotiankang2009@126.com

Keywords：

Chemokines factor receptors 4; Chemokines factor receptors 7; Gastric cancer; Immunohistochemistry; Prognosis

DOI：

10.7507/1007-9424.20150278

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the expressions and significance of chemokines factor receptors 4 (CXCR4) and chemokines factor receptors 7 (CXCR7) in gastric cancer tissues. Methods Sixty-five patients with gastric cancer who treated in our hospital from January 2011 to June 2013 were retrospectively collected as gastric cancer group, and 20 patients with gastric ulcer were retrospectively collected as control group at the same time. The expressions of CXCR4 and CXCR7 in gastric cancer tissues and normal gastric tissues were measured by immunohistochemistry, and then the relation-ship among expressions of CXCR4/CXCR7 in gastric cancer tissues and clinicopathological features of patients with gastric cancer was explored, as well as its effect on survival. Results Positive expression rates of CXCR4 and CXCR7 were identi-fied in 80.00% (52/65) and 84.62% (55/65) of the gastric cancer group, and 5.00% (1/20) and 10.00% (2/20) in control group respectively, and the positive expression rates of CXCR4 and CXCR7 in gastric cancer group were significantly higher than those of control group respectively (χ²=36.65, P<0.01; χ²=38.55, P<0.01). The positive expression rate of CXCR4 in gastric cancer tissues was related with degree of differentiation, T staging, and TNM staging (P<0.05), positive expression rate of CXCR4 in patients with poor differentiation, T3-4 staging, and TNM Ⅲ-Ⅳ staging were higher than corresponding patients with moderate/high degree of differentiation, T1-2 staging, and TNM Ⅰ-Ⅱ staging. The positive expression rate of CXCR7 in gastric cancer tissues was related with degree of differentiation, T staging, and N staging (P<0.05), positive expression rate of CXCR7 in patients with poor differentiation, T3-4 staging, and N1-3 staging were higher than corrsponding patients with moderate/high degree of differentiation, T1-2 staging, and N0 staging. The survival situation was worse in patients with positive expression of CXCR4 and CXCR7 than corresponding patients with negative expression (P=0.01, P=0.01) respectively. Conclusions CXCR4 and CXCR7 are related to gastric cancer genesis and development. Furthermore, the expressions of CXCR4 and CXCR7 could be used as markers to predict prognosis of gastric cancer. The regulation of CXCR4/chemokine ligand 12 (CXCL12) axis and CXCR7/CXCL12 axis may provide a new targeted therapy for patients with gastric cancer.

Citation： YANGJing, HUANGXian-bin, HAOXiang-yong, WEILi, JINGWu-tang, GUOTian-kang. Expressions and Clinical Significance of Chemokines Factor Receptors 4 and Chemokines Factor Receptors 7 in Gastric Cancer Tissues. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(9): 1062-1067. doi: 10.7507/1007-9424.20150278 Copy

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10.	Koshiba T, Hosotani R, Miyamoto Y, et al. Expression of stromal cell-derived factor 1 and CXCR4 ligand receptor system in pancreatic cancer:a possible role for tumor progression. Clin Cancer Res, 2000, 6(9):3530-3535.
11.	Edge SB, Compton CC. The American joint committee on cancer:the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol, 2010, 17(6):1471-1474.
12.	Yamaguchi R, Yano H, Nakashima O, et al. Expression of vascular endothelial growth factor-C in human hepatocellular carcinoma. J Gastroenterol Hepatol, 2006, 21(1 Pt 1):152-160.
13.	Strieter RM, Burdick MD, Gomperts BN, et al. CXC chemokines in angiogenesis. Cytokine Growth Factor Rev, 2005, 16(6):593-609.
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16.	Chatterjee S, Behnam Azad B, Nimmagadda S. The intricate role of CXCR4 in cancer. Adv Cancer Res, 2014, 124:31-82.
17.	Bonavia R, Bajetto A, Barbero S, et al. Chemokines and their recep-tors in the CNS:expression of CXCL12/SDF-1 and CXCR4 and their role in astrocyte proliferation. Toxicol Lett, 2003, 139(2-3):181-189.
18.	徐萌, 陳新明. 趨化因子及其受體在口腔鱗癌侵襲和轉移中的作用. 國外醫學:口腔醫學分冊, 2005, 32(3):204-206.
19.	Müller A, Homey B, Soto H, et al. Involvement of chemokine recep-tors in breast cancer metastasis. Nature, 2001, 410(6824):50-56.
20.	魏梅, 梁立治, 張昌卿, 等. 宮頸腺癌細胞CXCR4/CXCL12過表達與淋巴結轉移和慢性炎癥的關系. 癌癥, 2007, 26(3):298-302.
21.	Balabanian K, Lagane B, Infantino S, et al. The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes. J Biol Chem, 2005, 280(42):35760-35766.
22.	Burns JM, Summers BC, Wang Y, et al. A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med, 2006, 203(9):2201-2213.
23.	Luker KE, Gupta M, Steele JM, et al. Imaging ligand-dependent activation of CXCR7. Neoplasia, 2009, 11(10):1022-1035.
24.	Meijer J, Ogink J, Roos E. Effect of the chemokine receptor CXCR7 on proliferation of carcinoma cells in vitro and in vivo. Br J Cancer, 2008, 99(9):1493-1501.
25.	Iwakiri S, Mino N, Takahashi T, et al. Higher expression of chemo-kine receptor CXCR7 is linked to early and metastatic recurrence in pathological stageⅠnonsmall cell lung cancer. Cancer, 2009, 115 (11):2580-2593.
26.	Hao M, Zheng J, Hou K, et al. Role of chemokine receptor CXCR7 in bladder cancer progression. Biochem Pharmacol, 2012, 84(2):204-214.
27.	Satomura H, Sasaki K, Nakajima M, et al. Can expression of CXCL12 and CXCR4 be used to predict survival of gastric cancer patients?. Anticancer Res, 2014, 34(8):4051-4057.
28.	Nikzaban M, Hakhamaneshi MS, Fakhari S, et al. The chemokine receptor CXCR4 is associated with the staging of gastric cancer. Adv Biomed Res, 2014, 3(1):16.
29.	Kwak MK, Hur K, Park DJ, et al. Expression of chemokine receptors in human gastric cancer. Tumour Biol, 2005, 26(2):65-70.
30.	Masuda T, Nakashima Y, Ando K, et al. Nuclear expression of chemokine receptor CXCR4 indicates poorer prognosis in gastric cancer. Anticancer Res, 2014, 34(11):6397-6403.
31.	許統儉, 符煒, 徐為, 等. CXCR7與VEGF在胃癌組織中的表達及臨床意義. 江蘇醫藥, 2013, 39(13):1534-1536.
32.	師阿盟, 董蕾, 史海濤, 等. 趨化因子受體7在胃癌組織及細胞中的表達及意義. 南方醫科大學學報, 2014, 34(12):1780-1784.

1. ?衛生部統計信息中心. 2013中國衛生統計年鑒. 2014-04-26. http://www.nhfpc.gov.cn/htmlfiles/zwgkzt/ptjnj/year2013/index-2013.html.
2. 鄒小農, 孫喜斌, 陳萬青, 等. 2003-2007年中國胃癌發病與死亡情況分析. 腫瘤, 2012, 32(2):109-114.
3. 鄒文斌, 李兆申. 中國胃癌發病率及死亡率研究進展. 中國實用內科雜志, 2014, 34(4):408-415.
4. 段紀俊, 陳萬青, 張思維. 中國惡性腫瘤死亡率的國際比較. 中國社會醫學雜志, 2009, 26(6):377-378.
5. Schneider T, Ehrig K, Liewert I, et al. Interference with the CXCL12/CXCR4 axis as potential antitumor strategy:superiority of a sulfated galactofucan from the brown alga Saccharina latissima and Fucoidan over heparins. Glycobiology, 2015, 25(8):812-824.
6. Oishi S, Kuroyanagi T, Kubo T, et al. Development of novel CXC chemokine receptor 7 (CXCR7) ligands:selectivity Switch from CXCR4 antagonists with a cyclic pentapeptide scaffold. J Med Chem, 2015, 58(13):5218-5225.
7. Guillemot E, Karimdjee-Soilihi B, Pradelli E, et al. CXCR7 receptors facilitate the progression of colon carcinoma within lung not within liver. Br J Cancer, 2012, 107(12):1944-1949.
8. Monnier J, Boissan M, L'Helgoualc'h A, et al. CXCR7 is up-regulated in human and murine hepatocellular carcinoma and is specifically expressed by endothelial cells. Eur J Cancer, 2012, 48(1):138-148.
9. Lapteva N, Yang AG, Sanders DE, et al. CXCR4 knockdown by small interfering RNA abrogates breast tumor growth in vivo. Cancer Gene Ther, 2005, 12(1):84-89.
10. Koshiba T, Hosotani R, Miyamoto Y, et al. Expression of stromal cell-derived factor 1 and CXCR4 ligand receptor system in pancreatic cancer:a possible role for tumor progression. Clin Cancer Res, 2000, 6(9):3530-3535.
11. Edge SB, Compton CC. The American joint committee on cancer:the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol, 2010, 17(6):1471-1474.
12. Yamaguchi R, Yano H, Nakashima O, et al. Expression of vascular endothelial growth factor-C in human hepatocellular carcinoma. J Gastroenterol Hepatol, 2006, 21(1 Pt 1):152-160.
13. Strieter RM, Burdick MD, Gomperts BN, et al. CXC chemokines in angiogenesis. Cytokine Growth Factor Rev, 2005, 16(6):593-609.
14. Vandercappellen J, Van Damme J, Struyf S. The role of CXC chemo-kines and their receptors in cancer. Cancer Lett, 2008, 267(2):226-244.
15. Balkwill FR. The chemokine system and cancer. J Pathol, 2012, 226(2):148-157.
16. Chatterjee S, Behnam Azad B, Nimmagadda S. The intricate role of CXCR4 in cancer. Adv Cancer Res, 2014, 124:31-82.
17. Bonavia R, Bajetto A, Barbero S, et al. Chemokines and their recep-tors in the CNS:expression of CXCL12/SDF-1 and CXCR4 and their role in astrocyte proliferation. Toxicol Lett, 2003, 139(2-3):181-189.
18. 徐萌, 陳新明. 趨化因子及其受體在口腔鱗癌侵襲和轉移中的作用. 國外醫學:口腔醫學分冊, 2005, 32(3):204-206.
19. Müller A, Homey B, Soto H, et al. Involvement of chemokine recep-tors in breast cancer metastasis. Nature, 2001, 410(6824):50-56.
20. 魏梅, 梁立治, 張昌卿, 等. 宮頸腺癌細胞CXCR4/CXCL12過表達與淋巴結轉移和慢性炎癥的關系. 癌癥, 2007, 26(3):298-302.
21. Balabanian K, Lagane B, Infantino S, et al. The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes. J Biol Chem, 2005, 280(42):35760-35766.
22. Burns JM, Summers BC, Wang Y, et al. A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med, 2006, 203(9):2201-2213.
23. Luker KE, Gupta M, Steele JM, et al. Imaging ligand-dependent activation of CXCR7. Neoplasia, 2009, 11(10):1022-1035.
24. Meijer J, Ogink J, Roos E. Effect of the chemokine receptor CXCR7 on proliferation of carcinoma cells in vitro and in vivo. Br J Cancer, 2008, 99(9):1493-1501.
25. Iwakiri S, Mino N, Takahashi T, et al. Higher expression of chemo-kine receptor CXCR7 is linked to early and metastatic recurrence in pathological stageⅠnonsmall cell lung cancer. Cancer, 2009, 115 (11):2580-2593.
26. Hao M, Zheng J, Hou K, et al. Role of chemokine receptor CXCR7 in bladder cancer progression. Biochem Pharmacol, 2012, 84(2):204-214.
27. Satomura H, Sasaki K, Nakajima M, et al. Can expression of CXCL12 and CXCR4 be used to predict survival of gastric cancer patients?. Anticancer Res, 2014, 34(8):4051-4057.
28. Nikzaban M, Hakhamaneshi MS, Fakhari S, et al. The chemokine receptor CXCR4 is associated with the staging of gastric cancer. Adv Biomed Res, 2014, 3(1):16.
29. Kwak MK, Hur K, Park DJ, et al. Expression of chemokine receptors in human gastric cancer. Tumour Biol, 2005, 26(2):65-70.
30. Masuda T, Nakashima Y, Ando K, et al. Nuclear expression of chemokine receptor CXCR4 indicates poorer prognosis in gastric cancer. Anticancer Res, 2014, 34(11):6397-6403.
31. 許統儉, 符煒, 徐為, 等. CXCR7與VEGF在胃癌組織中的表達及臨床意義. 江蘇醫藥, 2013, 39(13):1534-1536.
32. 師阿盟, 董蕾, 史海濤, 等. 趨化因子受體7在胃癌組織及細胞中的表達及意義. 南方醫科大學學報, 2014, 34(12):1780-1784.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expressions and Clinical Significance of Chemokines Factor Receptors 4 and Chemokines Factor Receptors 7 in Gastric Cancer Tissues

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