MMP-2: More Than a Cancer Marker

Fri, 09/09/2016 - 14:36

Matrix metalloproteinases (MMP) are a family of endopeptidases involved in the breakdown of extracellular matrix (ECM) during both normal physiological and disease processes. MMP-2 is a zinc-dependent family member that selectively cleaves collagen and elastin, major structural components of the basement membrane. In addition, MMP-2 has been found to affect a number of non-matrix proteins such as big endothelin-1 (Fernandez-Patron et al., 1999), KISS (Takino et al., 2003), GSK3B (Kandasamy et al., 2009), and CHUK (Olivotto et al., 2013). This diverse activity has led MMP-2 to be linked to a wide variety of physiological processes.

While most MMP members must be proteolytically activated after secretion, MMP2 may be activated while still on the membrane. Specifically, pro-MMP-2 can be activated either extracellularly by proteases, or intracellularly via S-Glutathionylation (Okamoto et al., 2001). Researchers have speculated that MMP-2 activation by MMP-14/TIMP-2 facilitates effective tissue degradation and enhances tumor invasion and metastasis (Nishida et al., 2008), which accounts for the prevalent relationship between MMP2, cell proliferation and cancer progression.

Mutations in the MMP2 gene have been associated with Torg-Winchester syndrome, multicentric osteolysis, arthritis, and keloids.  Immunostaining with MMP2 antibodies has shown MMP2 likely plays a role in inflammation and cancer, as mentioned in a previous blog.

MMP-2 antibody MMP-2 antibody

IHC analysis of MMP-2 antibody (NB200-193) in human hepatocellular carcinoma tissue.

IHC analysis of MMP-2 antibody (NB200-114) in human ovary tissue.

Novus Biologicals offers a large selection of quality guaranteed antibodies that have been used in a wide variety of published research articles. Although these MMP-2 antibodies are most commonly used in cancer related research, a surprising number of papers cite using the antibody in vision related studies. For example, the MMP-2 antibody (NB200-193) was used to evaluate the level of MMP-2 and MMP-9 activities in patients with steroid induced posterior subcapsular cataracts. In another paper, MMP-2 antibody (NB200-114) was used as a proliferative marker to study the difference in proliferation abilities between central and peripheral retinal pigment epithelium.

Beyond cancer and vision studies, Novus' MMP-2 antibodies have been used in a number of metabolism related research studies. For instance, (NB200-113) has been used to study the effects of exercised-induced MMP stimulation in diabetes patients (Scheede-Bergdahl et al., 2014). Additionally, the MMP-2 antibody (AF1488) was used to study TIMP1 control of adipogenesis in obesity (Meissburger et al., 2011). Taken together, the use of Novus MMP-2 antibodies in these vision and metabolism studies demonstrate the diverse role that MMP-2 antibodies can hold in physiological research studies.

Novus Biologicals offers MMP-2 reagents for your research needs including:

Fernandez-Patron C, Radomski MW, Davidge ST. Vascular matrix metalloproteinase-2 cleaves big endothelin-1 yielding a novel vasoconstrictor. Circ Res. 1999 Nov 12;85(10):906-11. [PMID: 10559137]

Takino T, Koshikawa N, Miyamori H, Tanaka M, Sasaki T, Okada Y, Seiki M, Sato H. Cleavage of metastasis suppressor gene product KiSS-1 protein/metastin by matrix metalloproteinases. Oncogene. 2003 Jul 24;22(30):4617-26. [PMID: 12879005]

Kandasamy AD, Schulz R. Glycogen synthase kinase-3beta is activated by matrix metalloproteinase-2 mediated proteolysis in cardiomyoblasts. Cardiovasc Res. 2009 Sep 1;83(4):698-706. [PMID: 19493954]

Olivotto E, Otero M, Astolfi A, Platano D, Facchini A, Pagani S, Flamigni F, Facchini A, Goldring MB, Borzì RM, Marcu KB. IKKα/CHUK regulates extracellular matrix remodeling independent of its kinase activity to facilitate articular chondrocyte differentiation. PLoS One. 2013 Sep 2;8(9):e73024. [PMID: 24023802]

Okamoto T, Akaike T, Sawa T, Miyamoto Y, van der Vliet A, Maeda H. Activation of matrix metalloproteinases by peroxynitrite-induced protein S-glutathiolation via disulfide S-oxide formation. J Biol Chem. 2001 Aug 3;276(31):29596-602. [PMID: 11395496]

Nishida Y, Miyamori H, Thompson EW, Takino T, Endo Y, Sato H. Activation of matrix metalloproteinase-2 (MMP-2) by membrane type 1 matrix metalloproteinase through an artificial receptor for proMMP-2 generates active MMP-2. Cancer Res. 2008 Nov 1;68(21):9096-104. [PMID: 18974156]

Scheede-Bergdahl C, Bergdahl A, Schjerling P, Qvortrup K, Koskinen SO3, Dela F. Exercise-induced regulation of matrix metalloproteinases in the skeletal muscle of subjects with type 2 diabetes. Diab Vasc Dis Res. 2014 Sep;11(5):324-34. [PMID: 24903024]

Meissburger B, Stachorski L, Roder E, Rudofsky G, Wolfrum C. Tissue inhibitor of matrix metalloproteinase 1 (TIMP1) controls adipogenesis in obesity in mice and in humans. Diabetologia, 2011;54(6):1468-79. 2011 [PMID: 21437772]

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