Qin JC, Yu WT, Li HX, Liang YQ, Nong FF, Wen B. Cold exposure and capsaicin promote 1,2-dimethylhyrazine-induced colon carcinogenesis in rats correlates with extracellular matrix remodeling. World J Gastroenterol 2021; 27(39): 6615-6630 [PMID: 34754156 DOI: 10.3748/wjg.v27.i39.6615]
Corresponding Author of This Article
Bin Wen, PhD, Academic Research, Full Professor, Institute of Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, No. 12 Airport Road, Guangdong 530001, Guangdong Province, China. wenbin@gzucm.edu.cn
Research Domain of This Article
Oncology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
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/
Jing-Chun Qin, Yu-Qi Liang, Fei-Fei Nong, Bin Wen, Institute of Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangdong 530001, Guangdong Province, China
Jing-Chun Qin, Liuzhou People’s Hospital, Guangxi, 545006, Guangxi Province China
Wei-Tao Yu, Traditional Chinese Medicine Department, The Second People’s Hospital of Lianyungang, Lianyungang 222000, Jiangsu Province, China
Hui-Xuan Li, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, Guangdong 510000, Guangdong Province, China
Author contributions: Qin JC wrote the manuscript and performed the research; Wen B designed the study; Qin JC, Yu WT, Li HX, and Liang YQ conducted the experiments and analyzed the data; Nong FF reviewed and edited the manuscript; Wen B revised the manuscript.
Supported byNational Natural Science Foundation of China, No. 81673944.
Institutional animal care and use committee statement: The study was reviewed and approved by the Institutional Animal Ethics Committee of the Guangzhou University of Chinese Medicine (approval No. 20130001).
Conflict-of-interest statement: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled “Cold exposure and Capsaicin promote 1,2-dimethylhydrazine-induced colon carcinogenesis in rats correlates with extracellular matrix remodeling”.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at wenbin@gzucm.edu.cn. Participants gave informed consent for data sharing.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Corresponding author: Bin Wen, PhD, Academic Research, Full Professor, Institute of Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, No. 12 Airport Road, Guangdong 530001, Guangdong Province, China. wenbin@gzucm.edu.cn
Received: March 31, 2021 Peer-review started: April 1, 2021 First decision: June 24, 2021 Revised: July 2, 2021 Accepted: July 30, 2021 Article in press: July 30, 2021 Published online: October 21, 2021 Processing time: 190 Days and 4.6 Hours
Abstract
BACKGROUND
Extracellular matrix (ECM) remodeling and stiffening, which are correlated with tumor malignancy, drives tumor development. However, the relationship between ECM remodeling and rat experimental model of 1,2-dimethylhyrazine (DMH)-induced colorectal cancer (CRC) imposed by cold and capsaicin exposure remains unclear.
AIM
To explore the effects of cold exposure and capsaicin on ECM remodeling and ECM enzymes in DMH-induced CRC.
METHODS
For histopathological analysis, the sections of colon tissues were stained with hematoxylin and eosin, Masson’s trichrome, Picrosirius red, and Weigert’s Resorcin-Fuchsin to observe the remodeling of collagen and elastin. Additionally, the protein expression level of type I collagen (COL I), type 3 collagen (COL III0, elastin, matrix metalloproteinase (MMP) 1, MMP2, MMP9, and tissue-specific matrix metalloproteinase 1 (TIMP1) was assessed by immunohistochemistry. The messenger RNA (mRNA) levels of COL I, COL III, elastin, and lysyl oxidase-like-2 (LOXL2) in the colon tissues of rats was measured by reverse-transcriptase quantitative polymerase chain reaction.
RESULTS
Although no differences were observed in the proportion of adenomas, a trend towards the increase of invasive tumors was observed in the cold and capsaicin group. The cold exposure group had a metastasis rate compared with the other groups. Additionally, abnormal accumulation of both collagen and elastin was observed in the cold exposure and capsaicin group. Specifically, collagen quantitative analysis showed increased length, width, angle, and straightness compared with the DMH group. Collagen deposition and straightness were significantly increased in the cold exposure group compared with the capsaicin group. Cold exposure and capsaicin significantly increased the protein levels of COL I, elastin, and LOXL2 along with increases in their mRNA levels in the colon tissues compared with the DMH group, while COL III did not show a significant difference. Furthermore, in immunohistochemical evaluations, MMP1, MMP2, MMP9, and TIMP1 staining increased in the cold exposure and capsaicin group compared with the DMH group.
CONCLUSION
These results suggest that chronic cold and capsaicin exposure further increased the deposition of collagen and elastin in the colonic tissue. Increased COL I and elastin mRNA and protein levels expression may account for the enhanced ECM remodel and stiffness variations of colon tissue. The upregulated expression of the LOXL2 and physiological imbalance between MMP/TIMP activation and deactivation could contribute to the progression of the CRC resulting from cold and capsaicin exposure.
Core Tip: In this study, we discovered that remodeling of extracellular matrix (ECM) plays an important role in the progression of colorectal cancer (CRC). These results suggest that increased stiffness of colonic tissue and the remodeling of ECM mediated by ECM enzymes resulting from cold and capsaicin exposure predisposes an environment suitable for CRC development and progression. To target ECM in CRC tumor tissue could represent a novel potential therapeutic strategy.
