Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2020; 12(3): 267-275
Published online Mar 15, 2020. doi: 10.4251/wjgo.v12.i3.267
Changes in extracellular matrix in different stages of colorectal cancer and their effects on proliferation of cancer cells
Zhu-Lin Li, Zhen-Jun Wang, Guang-Hui Wei, Yong Yang, Xiao-Wan Wang
Zhu-Lin Li, Zhen-Jun Wang, Guang-Hui Wei, Yong Yang, Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
Xiao-Wan Wang, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China
Author contributions: Wang ZJ designed the experiments; Li ZL, Wei GH, Yang Y, and Wang XW performed the research; Li ZL wrote the paper.
Institutional review board statement: The study was reviewed and approved by Beijing Chaoyang Hospital, Capital Medical University.
Institutional animal care and use committee statement: All experimental manipulations were undertaken in accordance with the Guide for the Care and Use of Laboratory Animals (National Institutes of Health), and the study was approved by Beijing Vital River Laboratory Animal Technology Co, Ltd.
Conflict-of-interest statement: The authors report no relevant conflicts of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/
Corresponding author: Zhen-Jun Wang, MD, Chief Doctor, Professor, Surgeon, Surgical Oncologist, Department of General Surgery, Beijing Chaoyang Hospital. Capital Medical University, No.8 Gongti nan Lu, Chaoyang District, Beijing 100020, China. drzhenjun@163.com
Received: August 1, 2019
Peer-review started: August 1, 2019
First decision: August 27, 2019
Revised: January 12, 2020
Accepted: February 7, 2020
Article in press: February 7, 2020
Published online: March 15, 2020
Processing time: 224 Days and 7.2 Hours
Abstract
BACKGROUND

The extracellular matrix is the main component of the tumor microenvironment. Extracellular matrix remodels with the oncogenesis and development of tumors. Previous studies usually focused on the changes of proteins in normal colorectal tissues and colorectal cancers. Little is known about the changes in the extracellular matrix in different stages of colorectal cancer and the effects of these changes on the development of this cancer.

AIM

To test the changes of type I collagen, type IV collagen, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-3 (TIMP-3) in different stages of colorectal cancer and the effects of these changes on the proliferation of cancer cells.

METHODS

The extracellular matrix from various stages of colorectal cancer and normal colon tissue was obtained by using acellular technology. We used proteomics to detect the differential expression of proteins between normal colon tissues and colorectal cancer tissues, and then we used Western blot to observe their expression in each stage of colorectal cancer and in normal colon tissue. By co-culturing the extracellular matrix and HT29 colon cancer cells in vivo and in vitro, we tested the cancer cell proliferation rate in vitro by methyl thiazolyl tetrazolium (MTT) assay and in vivo by measuring the tumor volume.

RESULTS

The expression of type I collagen and MMP-2 increased with increased tumor stage. The expression of MMP-9 was higher in colorectal cancer tissues and was highest in stage III cancer. The expression of type IV collagen and TIMP-3 decreased with increased tumor stage. The proliferation rate of cancer cells in the extracellular matrix of colorectal cancer was higher than that in the extracellular matrix of the normal colon.

CONCLUSION

These data suggest that the extracellular matrix structure and composition become disorganized during the development of tumors, which is more conducive for the growth of cancer cells.

Keywords: Colorectal cancer; Extracellular matrix; MMP; Proliferation; Collagen; TIMP

Core tip: The extracellular matrix remodels during the occurrence and development of tumor. In order to study the changes of extracellular matrix, we obtained the extracellular matrix of colorectal cancer by acellular technology. We found that type I collagen, MMP-2, and MMP-9 increased in the colorectal cancer tissue, while type IV collagen and TIMP-3 decreased in the colorectal cancer tissue. Furthermore, we co-cultured the extracellular matrix and HT 29 cancer cells in vivo and in vitro, and found that the cancer extracellular matrix was more conducive for the growth of cancer cells than the normal tissue extracellular matrix.