Insights into the Role of Matrix Metalloproteinases in Precancerous Conditions and in Colorectal Cancer

Abstract

Colorectal cancer (CRC) is the third and second cancer for incidence and mortality worldwide, respectively, and is becoming prevalent in developing countries. Most CRCs derive from polyps, especially adenomatous polyps, which can gradually transform into CRC. The family of Matrix Metalloproteinases (MMPs) plays a critical role in the initiation and progression of CRC. Prominent MMPs, including MMP-1, MMP-2, MMP-7, MMP-8, MMP-9, MMP-12, MMP-13, MMP-14, and MMP-21, have been detected in CRC patients, and the expression of most of them correlates with a poor prognosis. Moreover, many studies have explored the inhibition of MMPs and targeted therapy for CRC, but there is not enough information about the role of MMPs in polyp malignancy. In this review, we discuss the role of MMPs in colorectal cancer and its pathogenesis

Amaryllidaceae Alkaloids Decrease the Proliferation, Invasion, and Secretion of Clinically Relevant Cytokines by Cultured Human Colon Cancer Cells

“…MMP-1, -2, -7, -9 and -13 are markers of poor colon cancer prognosis [ 49 ]. Each of these proteins digests a component of the extracellular matrix, facilitating the intravasation and extravasation of tumor cells [ 53 , 54 ]. Specifically, MMPs 1 and 13 are collagenase, MMP-2 is a gelatinase, and MMP-7 digests a wide variety of proteins including collagens, gelatins, laminin, proteoglycans, fibronectin, and elastin.…”

Pharmacologic Targeting of MMP2/9 Decreases Peritoneal Metastasis Formation of Colorectal Cancer in a Human Ex Vivo Peritoneum Culture Model

“…PC progression is a multi-step process that differs mechanistically from organ metastasis. We hypothesised that MMP2 and MMP9, both of which are relevant for ECM degradation, may be necessary for peritoneal invasion and cancer cell colonisation [ 18 , 19 , 20 ]. MMP2/9 gene expression levels were overexpressed in patient-derived primary CRC and corresponding PC samples.…”

“…Because MMPs played an essential role during PC formation in our model, we speculated that the inhibition of MMP2/9 could serve as an effective therapy to prevent PC at an early stage in patients with CRC [ 21 ]. Within the MMP family, both MMP2 and MMP9 belong to the gelatinases and possess overlapping functions [ 18 , 19 ]. Therefore, MMP2 and/or MMP9 might be involved in tumour cell invasion.…”

The potential mechanism of Longsheyangquan Decoction on the treatment of bladder cancer: Systemic network pharmacology and molecular docking

“…MMP9, a protein from the calcium-dependent zinc-containing endopeptidase family, is engaged in the degradation of extracellular matrix, especially type-IV collagen, resulting in multiple physiological and pathological processes, including tissue remodeling, angiogenesis, cell migration, rheumatoid arthritis, and tumor invasion ( Dufour et al, 2010 ; Xue et al, 2014 ; Li et al, 2021 ). Higher MMP9 expression is associated with a poorer prognosis for patients with breast cancer or colorectal cancer ( Dufour et al, 2011 ; Pezeshkian et al, 2021 ). PTGS2, also known as cyclooxygenase-2, converts arachidonic acid to prostaglandin endoperoxide H2 and engages in downstream inflammatory responses.…”