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

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 (n = 86), IBD-associated CRC (n = 23) and colorectal mucosa of non-tumor samples from IBD patients without (n = 47) and with (n = 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.

A CAF-Fueled TIMP-1/CD63/ITGB1/STAT3 Feedback Loop Promotes Migration and Growth of Breast Cancer Cells

“…TIMP-1-expressing CAFs are also found in other cancers. For instance, in colon cancer, TIMP-1-expressing CAFs are frequently present in those cancers associated with Crohn’s disease [ 61 ], a chronic inflammatory, IL-6-dependent disease [ 62 ]. Hence, the establishment of a TIMP-1/IL-6 loop to increase STAT3 activity may depend on cancer type and CAF subtype.…”

Expression of MMP-2, MMP-7, MMP-9, and TIMP-1 by Inflamed Mucosa in the Initial Diagnosis of Ulcerative Colitis as a Response Marker for Conventional Medical Treatment

“…An image analysis system with the Olympus BX51 microscope and soft analysis (analySIS, Soft imaging system, Münster, Germany) were used as follows: There were various optical thresholds for both stains. Each tissue section was scanned with a 400-power objective in two fields, as described previously [29, 30]. The fields were selected to search for the protein-reactive areas.…”

“…Fibroblast-like cells are spindle cells, while MICs are round cells. On the other hand, while epithelial cells are arranged to form either an acinar or trabecular pattern, stromal cells are propagated [29, 30].…”

Mechanisms of chemotherapeutic resistance and the application of targeted nanoparticles for enhanced chemotherapy in colorectal cancer

“…The induction of MMP activity contributes to the disassembly of intercellular junctions and the degradation and remodeling of the ECM. In this way, the distant colonization and growth of tumor cells are facilitated, and the physical limitations of cell motility are broken, allowing cells to participate in tumor invasion [ 19 , 51 ]. In addition to cytokines and chemokines, CAFs secrete abundant ECM stromal components that contribute to the formation of highly fibrotic tumor mesenchyme.…”