Characterization of a CAF-derived Factor as a Novel Therapeutic Target for Cancer Cachexia

Abstract

Cancer cachexia is a complex multifactorial syndrome characterized by unexpected weight loss and mainly associated with skeletal muscle wasting. This cachexia cannot be fully reversed by conventional nutritional support and leads functional deterioration of the musculature, along with reduced tolerance to chemotherapy and increased mortality. In this study, I profiled the secretory cytokines from cancer-stimulated cancer-associated fibroblasts (CAF) that harvested from colorectal cancer patient, a major component of the tumor microenvironment, and screened for their effects on skeletal muscle wasting. Using this approach, we characterized CAF-derived soluble factors CXCL-5 and IL-6 that induced the wasting phenotype in mouse skeletal myotubes synergically. CXCL-5 neutralizing antibody treatment reversed muscle atrophy effect in mouse, human skeletal myotubes. Based on these results, I suggest this CAF-secreted cytokine can be a new therapeutic target for cancer cachexia drug development.