Matrix Metalloproteinase Changes in a Cachectic Mouse Model

Abstract

Cardiac and skeletal muscle dysfunction is a recognized effect of cancer-induced cachexia. Cachexia is associated with changes in the heart, leading to clinical presentation of heart failure. In skeletal muscle, there is a decrease in myofiber diameter along with an inability to form new myoblasts. The ubiquitin system, responsible for marking proteins for degradation, has been implicated in the progression of cancer cachexia. Cachexia is a complex and multifaceted disease state with several potential contributors to the pathology. Matrix metalloproteinases (MMPS) are a family of enzymes capable of degrading components of the extracellular matrix (ECM) that may play a role in pathology common to cachexia. Changes to the ECM cause disruption in the connections between cells, at the basement membrane, and cell-to-cell interactions. In the present study, we used a murine model of cancer cachexia to determine if there are changes in gene expression of MMPs in striated muscle (Fig 1) and protein expression in striated muscle (Fig 2.) Because of the large number of MMPs, we narrowed down our analysis to MMP-2, -3, -9, and -14. These represent the MMPs that have been shown to contribute to both cardiac and skeletal muscle ECM changes. Our findings demonstrate a significant, increase in MMP protein and mRNA expression in cardiac and skeletal muscle. With these findings, MMPs represent a possible therapeutic avenue to treat cachexia associated with cancer.