MMP2: From Inflammation to Cancer

Fri, 12/13/2013 - 09:24

MMP2 is an extracellular matrix degradative peptidase enzyme that belongs to the large family of matrix metalloproteinases (MMPs) which each have different substrate specificities. Aberrant or derailed expression of various MMPs through loss of negative checks is strongly associated with tumor invasion, metastasis, and angiogenesis, as compared to tightly controlled physiological processes such as tissue remodeling, rebuilding, and embryonic development. MMP2 antibody immunostaining coupled with computed tomography is a viable prognostic indicator for small lung adenocarcinomas. Other indicators identified include CD34, MMP9, VEGF, and TIMP2 (1).  Breast cancer researchers used the MMP2 antibody in conjunction with thirteen other antibodies to generate detailed phenotypes of a large pool of basal breast cancer patient samples (2). They found that in this particular cancer subtype, only a subset of MMPs (MMP2 was not one of them) correlated with aggressive tumor behavior. Qian’s group used a xenograft nude mice system to investigate lung cancer cell invasiveness, and the MMP2 antibody was used to demonstrate that siRNA reduction of type 1 insulin-like growth factor receptor (IGF1R) inhibits metastases through an MMP2- and MMP9-dependent process (3). In addition to cancer models, MMP2 plays a role in inflammation and remodeling, as shown by Locke’s work in allergic airway disease (4). Locke employed the MMP2 antibody to more clearly define the sequence of remodeling events in acute, subacute, and chronic mouse models. Some interesting results in neuron axonal growth implicate chondroitin sulfate proteoglycans (CSPGs) as inhibitors and the MMP antibody enabled researchers to identify MMP2 as the molecule responsible for degrading CSPGs and therefore the inhibitory block, allowing nerve regeneration (5).

  1. PMID: 16153921
  2. PMID: 16627261
  3. PMID: 17277889
  4. PMID: 17237192
  5. PMID: 9651203

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