MMP12 Knockout Prevent Weight and Muscle Loss Induced by Cancer Cachexia

Abstract

AbstractWeight loss and muscle wasting can have devastating impacts on survival and quality of life of patients with cancer cachexia. Here, we have established a hybrid mouse of ApcMin/+ mice and MMP12 knockout mice (ApcMin/+; MMP12-/-) and found that knockout MMP12 can suppress the weight and muscle loss of ApcMin/+ mice. In detail, we found that interleukin 6 was highly upregulated in the serum of cancer patients and MMP12 was increased in muscle of tumor-bearing mice. Interestingly, the interleukin 6 secreted by tumor cells led to MMP12 overexpression in the macrophages, which further resulted in degradation of insulin and insulin-like growth factor 1 and interruption of glycolipid metabolism. Notably, depletion of MMP12 prevented weight loss of ApcMin/+ mice. Our study uncovers the critical role of MMP12 in controlling weight and highlights the great potential of MMP12 in the treatment of cancer cachexia.