Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 7, 2018; 24(5): 593-601
Published online Feb 7, 2018. doi: 10.3748/wjg.v24.i5.593
Promotion of Sema4D expression by tumor-associated macrophages: Significance in gastric carcinoma
Han Li, Jin-Shen Wang, Lin-Jun Mu, Ke-Shu Shan, Le-Ping Li, Yan-Bing Zhou
Han Li, Yan-Bing Zhou, Department of General Surgery, Affiliated Hospital of Qingdao University, Qingdao 266071, Shandong Province, China
Jin-Shen Wang, Ke-Shu Shan, Le-Ping Li, Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250012, Shandong Province, China
Lin-Jun Mu, Department of Emergency Surgery, Weifang People’s Hospital, Weifang 261000, Shandong Province, China
Author contributions: Li H and Wang JS contributed equally to this work; Li H, Wang JS, Mu LJ, Shan KS, Li LP and Zhou YB designed the research; Li H, Wang JS, Mu LJ and Shan KS performed the research; Li H, Wang JS, Mu LJ and Shan KS analyzed the data; Li H, Wang JS, Mu LJ, Shan KS and Li LP wrote the manuscript.
Institutional review board statement: This manuscript has been reviewed and certified by the local institutional review board.
Conflict-of-interest statement: The authors declare no conflict of interest related to this publication.
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: Yan-Bing Zhou, PhD, Chief Doctor, Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University, Qingdao 266071, Shandong Province, China. didi8114@163.com
Telephone: +86-531-68776388 Fax: +86-531-68776388
Received: August 26, 2017
Peer-review started: August 27, 2017
First decision: September 12, 2017
Revised: September 26, 2017
Accepted: November 21, 2017
Article in press: November 21, 2017
Published online: February 7, 2018
Processing time: 157 Days and 16.1 Hours
Abstract
AIM

To study the role of semaphorin 4D (Sema4D) expression promoted by tumor-associated macrophages (TAMs) in gastric carcinoma cells and its clinical significance in the invasion and metastasis of gastric carcinoma.

METHODS

CD68 and Sema4D expression was analyzed in gastric carcinoma and adjacent normal tissues from 290 patients using the immunohistochemical streptavidin-peroxidase method, and their relationships with clinicopathological features were evaluated. Human M2 macrophages were induced in vitro and co-cultured in non-contact with gastric carcinoma SGC-7901 cells. Changes in the secretory Sema4D level in the SGC-7901 cell supernatant were measured using an enzyme-linked immunosorbent assay. The effects of TAMs on SGC-7901 cell invasion and migration were assessed with invasion and migration assays, respectively.

RESULTS

CD68 and Sema4D protein expression was significantly higher in gastric carcinoma tissues than in adjacent normal tissues (71.7% vs 33.8% and 74.5% vs 42.8%, respectively; P < 0.01). CD68 and Sema4D protein expression was significantly associated with histological differentiation, TNM stage, and lymph node metastasis (P < 0.05), and their expression levels were positively correlated with one another (r = 0.467, P < 0.01). In the in vitro experiment, secretory Sema4D protein expression was significantly increased in the supernatant of SGC-7901 cells co-cultured with TAMs compared with the blank control (1224.13 ± 29.43 vs 637.15 ± 33.84, P < 0.01). Cell invasion and metastasis were enhanced in the Transwell invasion and migration assays (P < 0.01).

CONCLUSION

TAMs promote the invasion and metastasis of gastric carcinoma cells possibly through upregulated secretory Sema4D protein expression. Combined detection of TAM markers, CD68 and Sema4D, in gastric carcinoma tissue shows potential to predict the trend of gastric carcinoma progression.

Keywords: Gastric carcinoma; CD68; Semaphorin 4D; Tumor-associated macrophages

Core tip: This study explored the role and clinical significance of semaphorin 4D (Sema4D) expression promoted by tumor-associated macrophages (TAMs) in gastric carcinoma cells. By using immunohistochemical streptavidin-peroxidase method on tissue species and gastric carcinoma cells in non-contact co-culture with human M2 macrophages in vitro, we found that Sema4D protein expression was significantly higher in gastric carcinoma tissues than in adjacent normal tissues, and TAMs promoted the invasion and metastasis of gastric carcinoma cells possibly through upregulated Sema4D protein expression.