Tumor Secreted Autocrine Motility Factor (AMF): Causal Role in an Animal Model of Cachexia

摘要

Cancer cachexia has three clinical features: (1) loss of appetite (anorexia), (2) nutritional mal-absorption, and (3) muscle and fat wasting caused by tumor-stimulated factors. This project focused on muscle wasting A number of factors have been proposed to cause cancer cachexia. Lack of progress in the area is unfortunate, given the tremendous benefit patients with advanced cancer would receive from effective treatment of cachexia to improve quality of life and postpone mortality. We proposed that autocrine motility factor (AMF) is released into the bloodstream from cancer sites and stimulates muscle wasting. During the grant period we: (1) Established an animal model in which CHO/AMF tumors caused cachexia in mice; (2) Showed that injection of recombinant AMF protein caused significant weight loss in mice in 24 hours; (3) Solved the 3-D structures of mouse and human proteins; (4) Initiated characterization of the genes involved in muscle protein degradation in response to cachexia in the mouse model with CHO/AMF tumors.