Published online Oct 21, 2021. doi: 10.3748/wjg.v27.i39.6615
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
Colorectal cancer (CRC) is a cancer with high prevalence and mortality in the world. Extracellular matrix (ECM) is a dynamic compartment that regulates tissue develop
To identify the effect of cold exposure and capsaicin on ECM remodeling, ECM enzymes, and the underlying mechanism.
To explore the role of ECM remodeling and ECM enzymes in the 1,2-dimethylhydrazine (DMH)-induced CRC progression and the underlying mechanism.
The CRC rat model was conducted by adding DMH and examining the role of ECM remodeling and ECM enzymes on DMH-induced CRC in the model. We investigated the morphology and structure of collagen and elastin using Masson’s trichrome, Picrosirius red, and Weigert’s Resorcin-Fuchsin stains. Additionally, we evaluated the protein expression level of type I collagen (COL I), type III collagen (COL III), elastin, lysyl oxidase-like 2 (LOXL2), matrix metalloproteinase (MMP) 1, MMP2, MMP9, and tissue-specific matrix metalloproteinase 1 by immunohistochemistry and observed the expression of COL I, COL III, elastin, and LOXL2 in the colon tissues of rats by reverse-transcriptase quantitative polymerase chain reaction.
We found that although there were no differences in the proportion of adenomas, a trend towards the increase of invasive tumors was observed in the cold and capsaicin group. Cold exposure group had a metastasis rate comparative 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 messenger RNA 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 tissue-specific matrix metalloproteinase 1 staining increased in the cold exposure and capsaicin group compared with the DMH group.
Increased stiffness of colonic tissue and the remodeling of ECM mediated by ECM enzymes resulted from cold and capsaicin exposure, predisposing an environment suitable for CRC development and progression.
To target ECM in CRC tumor tissue could represent a novel potential therapeutic strategy.