Untitled

Abstract

The role of various matrix metalloproteinases (MMP)--such as gelatinases, stromelysins, matrilysin, collagenase-3, and membrane-bound MMP (MB-MMP)--in tumor invasion and metastasis is discussed. Data suggesting significance for malignant growth of the expression level of these enzymes and also of their activators and inhibitors are presented. It is concluded that at different stages of tumor progression the activity of different MMPs is displayed, which is regulated by various growth factors and oncogenes. Different malignancies are characterized by changes in activities of specific MMPs. Data are presented which show significance of the ratio between the MMP activity and that of tissue inhibitors of metalloproteinases (TIMP) in tumor invasion and metastasis, especially in connection with a dual role of TIMP as both MMP inhibitors and activators.

Baicalein Inhibits the Migration and Invasion of B16F10 Mouse Melanoma Cells through Inactivation of the PI3K/Akt Signaling Pathway

“…MMPs that are highly expressed in various malignant tumors have been recognized as playing an important role in cell motility and invasion via the degradation of ECM components of blood or lymph vessels (Khasigov et al ., 2003; Hanahan and Weinberg, 2011). Gelatinase types of MMPs such as MMP-2 and -9 promote tumor cell invasion in various cancer cell lines because of their ability to degrade various types of collagens (Vu and Werb, 2000; Egeblad and Werb, 2002).…”

“…Metastasis is a highly coordinated multistep process, of which degradation of the extracellular matrix (ECM) is an important component (Khasigov et al ., 2003; Hanahan and Weinberg, 2011). Through degradation of the ECM, cancer cells escape the primary tumor, penetrate the basement membrane of capillary and lymphatic vessels, intravasate, and migrate to new locations in the body (Yilmaz et al ., 2007; Valastyan and Weinberg, 2011).…”

“…Through degradation of the ECM, cancer cells escape the primary tumor, penetrate the basement membrane of capillary and lymphatic vessels, intravasate, and migrate to new locations in the body (Yilmaz et al ., 2007; Valastyan and Weinberg, 2011). Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, are crucial molecules in the degradation of ECM and affect the invasion of cancer cells (Khasigov et al ., 2003; Kessenbrock et al ., 2010). Among the MMPs, MMP-2 (gelatinase A) and -9 (gelatinase B) play pivotal roles in the process of ECM degradation (Vu and Werb, 2000; Egeblad and Werb, 2002).…”

Gomisin A Suppresses Colorectal Lung Metastasis by Inducing AMPK/p38-Mediated Apoptosis and Decreasing Metastatic Abilities of Colorectal Cancer Cells

“…Additionally, the results of the invasion assay showed that the invasion of CT26 and HT29 cells was attenuated by G.A treatment ( Figure 7C ). The gelatinase activity of MMP-2 and MMP-9 is closely related to the invasiveness of cancer cells (Khasigov et al, 2003). We observed that G.A reduced the expression levels of MMP-2 and MMP-9 using IF analysis ( Figure 7D ).…”

“…A typical feature of EMT is the loss of cell-cell contact by the regulation of expression of cell-cell adhesion molecules such as E-cadherin, N-cadherin, and vimentin (Thiery and Sleeman, 2006). Additionally, epithelial cancer cells become spindle shaped with increased metastatic abilities including migration and invasion by enhancing matrix metalloproteinase (MMP)-2 and MMP-9 production, which are involved in matrix remodeling-related proteolysis (Khasigov et al, 2003). …”