Matrix metalloproteinases in tumor invasion: Role for cell migration

Abstract

Matrix metalloproteinases (MMP) play a role in a wide range of tumorigenesis, including early carcinogenesis events, tumor growth and tumor invasion and metastasis. Given that the ability of tumor cells to infiltrate and disseminate widely is what makes the tumors malignant, a role of MMP in cell migration during this invasive and metastatic process is important. There are two types of cancer cell migration: single cell locomotion and cohort migration (cell movement en mass keeping cell-cell contact, which is frequently seen in better differentiated carcinomas). Cell surface localization and activation of MMP is essential for cells to migrate, through rearrangement of extracellular matrix (ECM) to suit cell migration. Certain MMP, such as gelatinases and membrane -type 1 MMP, have special mechanisms to localize at leading edges in both types of cell migration. Moreover, in cohort migration, expression of these MMP is regulated via cell-cell contact within migrating cell sheets and confined to the foremost pathfinder cells of the migrating cell sheets. New roles of cell surface MMP, such as cleavage of cell surface receptors or cofactors involved in cell-ECM interactions during cell migration, are also discussed.

Snail accelerates cancer invasion by upregulating MMP expression and is associated with poor prognosis of hepatocellular carcinoma

“…We further discovered that MMP-1, MMP-2, MMP-7, and MT1-MMP expressions were significantly upregulated by Snail introduction (Miyoshi et al, 2004). The MMP family is known to play a key role in tumour invasion of various human r = 0.256 cancers including HCC (Yamamoto et al, 1997;Harada et al, 1998;Nabeshima et al, 2002). Increased expression of MMP-2, MMP-7, and MT1-MMP had a strong association with dedifferentiation, portal invasion, intrahepatic metastasis, and recurrence in HCC (Yamamoto et al, 1997;Harada et al, 1998).…”

Immunohistochemical expression of MMPs 1, 7, and 26 in syndrome and nonsyndrome odontogenic keratocysts

“…1,3,11 Remodeling the epithelial basement membrane is a crucial step in many processes, from injury healing and keratinocyte migration 20 to tumor invasion and metastasis. 15 Many extracellular matrix substrates for matrilysins are epithelial and vascular basement membrane components, such as, laminin, fibronectin, and type IV collagen. 2,12,35 Thus, the immunoreactivity of the SOKC and NSOKC epithelial cells to MMPs-7 and Ϫ26 observed in this research corroborate the results reported by other studies that analyzed basement membrane composition in the OKC epithelial-connective tissue junction.…”

“…26,27 MMPs-2 and Ϫ9, also known as gelatinases, are important proteases that degrade the components present both in basement membranes, such as type IV collagen and laminin, 15,36 and in the interstitial extracellular matrix, particularly the fragments derived from the proteolysis of type I fibrillar collagen, denominated gelatins. 18,36 MMP-2 has been observed by immunohistochemistry in OKC epithelial basement membranes, 33 by in situ hybridization in OKC connective tissue fibroblasts, 33 by western immunoblotting and gelatin zymography in cultured fibroblasts, 32 and in co-cultured OKC epithelial cells and fibroblasts.…”

“…Thus, MMPs not only promote extracellular matrix degradation but also regulate signals emitted by matrix molecules, which regulate proliferation, differentiation, and cell death. [13][14][15] MMP-1 (collagenase-1, interstitial collagenase), synthesized by a wide variety of normal cells, such as fibroblasts, macrophages, and endothelial and epithelial cells, is one of the major proteases that can degrade the triple-helical domain of type I fibrillar collagen. [16][17][18] Type I collagen, responsible for connective tissue strength and rigidity, is the main component of the organic bone matrix.…”

Association of a single nucleotide polymorphism in the matrix metalloproteinase‐1 promoter with glioblastoma

“…MMP-1 protein levels increase with increasing tumor grade and correlate with increased glioma invasiveness. [12][13][14][15][16] In the absence of significant quantities of collagen in normal brain or brain tumor tissue, recent attention has focused on the ability of MMPs to act enzymatically on other ECM components and pro-forms of specific cytokines.A functional single nucleotide polymorphism (SNP) is known to occur at position 21607 in the MMP-1 promoter. 17 It consists of either the presence or absence of a guanine nucleotide adjacent to a preexisting guanine nucleotide at 21606.…”