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金属蛋白酶-7和-14与金属蛋白酶组织抑制剂1在黏膜基质细胞中的表达及炎症性肠病中结直肠癌发生发展的关系

Relationship between Metalloprotease-7 and -14 and Tissue Inhibitor of Metalloprotease 1 Expression by Mucosal Stromal Cells and Colorectal Cancer Development in Inflammatory Bowel Disease.

作者信息

Altadill Antonio, Eiro Noemi, González Luis O, Andicoechea Alejandro, Fernández-Francos Silvia, Rodrigo Luis, García-Muñiz José Luis, Vizoso Francisco J

机构信息

Department of Internal Medicine, Fundación Hospital de Jove, Avda. Eduardo Castro, 161, 33290 Gijón, Spain.

Research Unit, Fundación Hospital de Jove, Avda. Eduardo Castro, 161, 33290 Gijón, Spain.

出版信息

Biomedicines. 2021 Apr 30;9(5):495. doi: 10.3390/biomedicines9050495.

DOI:10.3390/biomedicines9050495
PMID:33946534
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8147221/
Abstract

Colorectal carcinoma (CRC) associated with inflammatory bowel disease (IBD) is an example of an inflammation-related cancer. Matrix metalloproteases (MMP) are known to be associated with both processes. The aim of the study was to compare the expression of MMP-7, MMP-14 and tissue inhibitor of metalloproteases-1 (TIMP-1) in sporadic CRC- and IBD-associated CRC, and to compare the expression in inflamed and non-inflamed colonic tissue samples from IBD patients without or with associated CRC. An immunohistochemical study of MMP-7, -14 and TIMP-1 was performed on sporadic CRC ( = 86), IBD-associated CRC ( = 23) and colorectal mucosa of non-tumor samples from IBD patients without ( = 47) and with ( = 23) associated CRC. These factors were more frequently expressed by cancer-associated fibroblasts (CAF) from IBD-associated CRC than by CAF from CRC not associated with IBD. Regarding the inflamed tissue of IBD patients, Crohn's disease (CD) patients with CRC development showed a higher expression of MMP-14 by fibroblasts and by mononuclear inflammatory cells (MICs) than CD patients without CRC development. In non-inflamed tissue samples, MMP-7 associated with fibroblasts and MICs, and TIMP-1 associated with MICs, were more frequently expressed in CD patients with CRC development than in CD patients without CRC development. Our data suggest that these factor expressions by stromal cells may be biological markers of CRC development risk in IBD patients.

摘要

与炎症性肠病(IBD)相关的结直肠癌(CRC)是炎症相关癌症的一个例子。已知基质金属蛋白酶(MMP)与这两个过程都有关联。本研究的目的是比较散发性CRC和IBD相关CRC中MMP - 7、MMP - 14和金属蛋白酶组织抑制剂 - 1(TIMP - 1)的表达,并比较无CRC或有CRC的IBD患者发炎和未发炎结肠组织样本中的表达。对散发性CRC(n = 86)、IBD相关CRC(n = 23)以及无(n = 47)CRC和有(n = 23)CRC的IBD患者非肿瘤样本的结肠黏膜进行了MMP - 7、-14和TIMP - 1的免疫组织化学研究。与不伴有IBD的CRC中的癌相关成纤维细胞(CAF)相比,IBD相关CRC中的CAF更频繁地表达这些因子。关于IBD患者的发炎组织,发生CRC的克罗恩病(CD)患者的成纤维细胞和单核炎症细胞(MIC)中MMP - 14的表达高于未发生CRC的CD患者。在未发炎的组织样本中,与成纤维细胞和MIC相关的MMP - 7以及与MIC相关的TIMP - 1在发生CRC的CD患者中比在未发生CRC的CD患者中更频繁地表达。我们的数据表明,基质细胞的这些因子表达可能是IBD患者发生CRC风险的生物学标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/8147221/4d8f40a28df0/biomedicines-09-00495-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/8147221/520aa1c5ebde/biomedicines-09-00495-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/8147221/4d8f40a28df0/biomedicines-09-00495-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/8147221/520aa1c5ebde/biomedicines-09-00495-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/8147221/4d8f40a28df0/biomedicines-09-00495-g002.jpg

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