Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2017; 23(17): 3053-3065
Published online May 7, 2017. doi: 10.3748/wjg.v23.i17.3053
CXCR7/CXCL12 axis is involved in lymph node and liver metastasis of gastric carcinoma
Qi Xin, Na Zhang, Hai-Bo Yu, Qin Zhang, Yan-Fen Cui, Chuan-Shan Zhang, Zhe Ma, Yan Yang, Wei Liu
Qi Xin, Qin Zhang, Chuan-Shan Zhang, Zhe Ma, Department of Pathology, Tianjin Third Central Hospital, Tianjin Key Laboratory of Artificial Cells, Tianjin 300170, China
Qi Xin, Qin Zhang, Chuan-Shan Zhang, Zhe Ma, The Third Central Clinical College of Tianjin Medical University, Tianjin 300170, China
Na Zhang, Yan Yang, Wei Liu, Department of Pathology, Dagang Hospital, Tianjin 300270, China
Hai-Bo Yu, The Second Hospital of Tianjin Medical University, Tianjin 300211, China
Yan-Fen Cui, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300070, China
Author contributions: Xin Q, Zhang N and Yu HB contributed equally to this work; Xin Q, Zhang N and Yu HB designed the research; Xin Q, Cui YF, Ma Z, Yang Y and Liu W performed the research; Yu HB and Zhang CS contributed new reagents or analytic tools; Xin Q, Zhang N and Yu HB analyzed the data; Xin Q and Zhang Q wrote the paper.
Supported by the Tianjin Binhai New Area Health Industry Medical and Health Science Project, No. 2011BHKY021; Tianjin Binhai New Area Science and Technology Development Strategy Research Project, No. 2012DK15W007; and Tianjin Binhai New Area Port Area Social Development Science and Technology Project, No. 20120211.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Tianjin Third Central Hospital, Tianjin, China.
Conflict-of-interest statement: The authors declare no competing financial interests and have no conflicts of interest to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Na Zhang, Department of Pathology, Dagang Hospital, Tianjin Binhai New Area, Tianjin 300211, China. 13802108605@163.com
Telephone: +86-22-84112490
Received: December 13, 2016
Peer-review started: December 16, 2016
First decision: December 29, 2016
Revised: January 17, 2017
Accepted: March 20, 2017
Article in press: March 20, 2017
Published online: May 7, 2017
Processing time: 143 Days and 21.7 Hours
Abstract
AIM

To investigate the role of CXC chemokine receptor (CXCR)-7 and CXCL12 in lymph node and liver metastasis of gastric carcinoma.

METHODS

In 160 cases of gastric cancer, the expression of CXCR7 and CXCL12 in tumor and matched tumor-adjacent non-cancer tissues, in the lymph nodes around the stomach and in the liver was detected using immunohistochemistry to analyze the relationship between CXCR7/CXCL12 expression and clinicopathological features and to determine whether CXCR7 and CXCL12 constitute a biological axis to promote lymph node and liver metastasis of gastric cancer. Furthermore, the CXCR7 gene was silenced and overexpressed in human gastric cancer SGC-7901 cells, and cell proliferation, migration and invasiveness were measured by the MTT, wound healing and Transwell assays, respectively.

RESULTS

CXCR7 expression was up-regulated in gastric cancer tissues (P = 0.011). CXCR7/CXCL12 expression was significantly related to high tumor stage and lymph node (r = 0.338, P = 0.000) and liver metastasis (r = 0.629, P = 0.000). The expression of CXCL12 in lymph node and liver metastasis was higher than that in primary gastric cancer tissues (χ2 = 6.669, P = 0.010; χ2 = 25379, P = 0.000), and the expression of CXCL12 in lymph node and liver metastasis of gastric cancer was consistent with the positive expression of CXCR7 in primary gastric cancer (r = 0.338, P = 0.000; r = 0.629, P = 0.000). Overexpression of the CXCR7 gene promoted cell proliferation, migration and invasion. Silencing of the CXCR7 gene suppressed SGC-7901 cell proliferation, migration and invasion. Human gastric cancer cell lines expressed CXCR7 and showed vigorous proliferation and migratory responses to CXCL12.

CONCLUSION

The CXCR7/CXCL12 axis is involved in lymph node and liver metastasis of gastric cancer. CXCR7 is considered a potential therapeutic target for the treatment of gastric cancer.

Keywords: Gastric cancer; Lymph node metastasis; Stromal cell derived factor-1; Liver metastasis; CXC chemokine receptor-7

Core tip: The CXC chemokine receptor (CXCR)-7/CXCL12 axis could play an important role in metastasis of certain cancers. However, little is known about the effect of CXCR7/CXCL12 on the process of gastric cancer. This study investigated the role of CXCL12 and CXCR7 in lymph node and liver metastasis of gastric carcinoma. We found that the CXCR7/CXCL12 axis was involved in the lymph node and liver metastasis of gastric cancer. Overexpression of the CXCR7 gene promoted cell proliferation, migration and invasion. Silencing of the CXCR7 gene suppressed these processes. CXCR7 was considered a potential therapeutic target for the treatment of gastric cancer.