Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2017; 23(28): 5167-5178
Published online Jul 28, 2017. doi: 10.3748/wjg.v23.i28.5167
Fibroblast-derived CXCL12/SDF-1α promotes CXCL6 secretion and co-operatively enhances metastatic potential through the PI3K/Akt/mTOR pathway in colon cancer
Jia-Chi Ma, Xiao-Wen Sun, He Su, Quan Chen, Tian-Kang Guo, Yuan Li, Xiao-Chang Chen, Jin Guo, Zhen-Qiang Gong, Xiao-Dan Zhao, Jian-Bo Qi
Jia-Chi Ma, He Su, Quan Chen, Tian-Kang Guo, Yuan Li, Xiao-Chang Chen, Jin Guo, Zhen-Qiang Gong, Xiao-Dan Zhao, Jian-Bo Qi, Department of General Surgery, Gansu Provincial People’s Hospital, Lanzhou 730000, Gansu Province, China
Xiao-Wen Sun, Department of Dermatology, The First Hospital of Tianshui, Tianshui 741000, Gansu Province, China
Xiao-Chang Chen, Jin Guo, Zhen-Qiang Gong, Xiao-Dan Zhao, Ningxia Medical University, Yinchuan 750000, Ningxia Hui Autonomous Region, China
Jian-Bo Qi, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, Gansu Province, China
Author contributions: Ma JC and Sun XW contributed equally to this article; Su H, Chen Q and Guo TK conceived and designed the study; Li Y, Chen XC, Gong ZQ, Zhao XD and Qi JB performed the experiments; Ma JC, Su H, Chen Q, Chen XC, Guo J and Gong ZQ analyzed and interpreted the data; Ma JC and Sun XW drafted the manuscript.
Supported by National Natural Science Foundation of China, No. 81260325 (to Ma JC).
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: No additional unpublished data are available.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: Jia-Chi Ma, PhD, Department of General Surgery, Gansu Provincial People’s Hospital, 204 Dong Gang West Road, Lanzhou 730000, Gansu Province, China. tsmjc@hotmail.com
Telephone: +86-931-8281382
Received: February 10, 2017
Peer-review started: February 14, 2017
First decision: March 30, 2017
Revised: April 13, 2017
Accepted: May 9, 2017
Article in press: May 9, 2017
Published online: July 28, 2017
Abstract
AIM

To investigate the underlying mechanism by which CXCL12 and CXCL6 influences the metastatic potential of colon cancer and internal relation of colon cancer and stromal cells.

METHODS

Western blotting was used to detect the expression of CXCL12 and CXCL6 in colon cancer cells and stromal cells. The co-operative effects of CXCL12 and CXCL6 on proliferation and invasion of colon cancer cells and human umbilical vein endothelial cells (HUVECs) were determined by enzyme-linked immunosorbent assay, and proliferation and invasion assays. The angiogenesis of HUVECs through interaction with cancer cells and stromal cells was examined by angiogenesis assay. We eventually investigated activation of PI3K/Akt/mTOR signaling by CXCL12 involved in the metastatic process of colon cancer.

RESULTS

CXCL12 was expressed in DLD-1 cancer cells and fibroblasts. The secretion level of CXCL6 by colon cancer cells and HUVECs were significantly promoted by fibroblasts derived from CXCL12. CXCL6 and CXCL2 could significantly enhance HUVEC proliferation and migration (P < 0.01). CXCL6 and CXCL2 enhanced angiogenesis by HUVECs when cultured with fibroblast cells and colon cancer cells (P < 0.01). CXCL12 also enhanced the invasion of colon cancer cells. Stromal cell-derived CXCL12 promoted the secretion level of CXCL6 and co-operatively promoted metastasis of colon carcinoma through activation of the PI3K/Akt/mTOR pathway.

CONCLUSION

Fibroblast-derived CXCL12 enhanced the CXCL6 secretion of colon cancer cells, and both CXCL12 and CXCL6 co-operatively regulated the metastasis via the PI3K/Akt/mTOR signaling pathway. Blocking this pathway may be a potential anti-metastatic therapeutic target for patients with colon cancer.

Keywords: CXCL12/SDF-1α, CXCL6, Metastasis, PI3K/Akt/mTOR pathway, Colon cancer

Core tip: This study has provided the first report of fibroblast-derived CXCL12 enhancement of CXCL6 secretion in colon cancer cells, and of both CXCL12 and CXCL6 co-operatively regulating metastasis through the PI3K/Akt/mTOR signaling pathway. Blockage of this pathway may be a potential anti-metastatic therapeutic target for patients with colon cancer. Our work might encourage further investigation into more potent angiogenesis modulating agents to improve the effectiveness of colon cancer therapies.