Many patients with cancer experience cachexia, a wasting disorder of adipose tissue and skeletal muscle that leads to weight loss and frailty; now, tumour-derived parathyroid-hormone-related protein has been shown to stimulate the expression of genes involved in heat production in adipose tissues and to have an important role in tissue wasting. Many cancer patients suffer from cachexia — a wasting disorder of adipose tissue and skeletal muscle leading to weight loss and frailty. A key characteristic of cachexia is increased energy expenditure, thought to be the result of elevated thermogenic activity of brown fat. In experiments with the Lewis lung carcinoma mouse model, Bruce Spiegelman and colleagues demonstrate that tumour-derived parathyroid-hormone-related protein (PTHrP) stimulates thermogenic gene expression in adipose tissues and plays an important role in tissue wasting. Neutralization of PTHrP blocks fat browning and halts muscle wasting . In an evaluation of 47 patients with cancer, the authors identified a PTHrP-positive subset, raising the possibility that targeting PTHrP might help to limit cancer cachexia and improve patient survival. Cachexia is a wasting disorder of adipose and skeletal muscle tissues that leads to profound weight loss and frailty. About half of all cancer patients suffer from cachexia, which impairs quality of life, limits cancer therapy and decreases survival. One key characteristic of cachexia is higher resting energy expenditure levels than in healthy individuals, which has been linked to greater thermogenesis by brown fat1,2,3,4,5,6. How tumours induce brown fat activity is unknown. Here, using a Lewis lung carcinoma model of cancer cachexia, we show that tumour-derived parathyroid-hormone-related protein (PTHrP) has an important role in wasting, through driving the expression of genes involved in thermogenesis in adipose tissues. Neutralization of PTHrP in tumour-bearing mice blocked adipose tissue browning and the loss of muscle mass and strength. Our results demonstrate that PTHrP mediates energy wasting in fat tissues and contributes to the broader aspects of cancer cachexia. Thus, neutralization of PTHrP might hold promise for ameliorating cancer cachexia and improving patient survival.

Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia