Abstract
Factors secreted from tumors/tumor cells are hypothesized to cause skeletal muscle wasting in cancer patients. We examined whether cancer cells secrete factors to promote atrophy by evaluating the effects of conditioned media (CM) from murine lung cancer cells and primary cultures of human lung tumor cells on cultured myotubes. We evaluated murine Lewis lung carcinoma (LLC) and KRASG12D cells, and primary cell lines derived from tumor biopsies from patients with lung cancer (hTCM; n = 6). In all experiments, serum content was matched across treatment groups. We hypothesized that CM from murine and human tumor cells would reduce myotube myosin content, decrease mitochondrial content, and increase mitochondrial reactive oxygen species (ROS) production. Treatment of myotubes differentiated for 7 days with CM from LLC and KRASG12D cells did not alter any of these variables. Effects of murine tumor cell CM were observed when myotubes differentiated for 4 days were treated with tumor cell CM and compared with undiluted differentiation media. However, these effects were not apparent if tumor cell CM treatments were compared with control cell CM or dilution controls. Finally, CM from human lung tumor primary cell lines did not modify myosin content or mitochondrial content or ROS production compared with either undiluted differentiated media, control cell CM, or dilution controls. Our results do not support the hypothesis that factors released from cultured lung cancer/tumor cells promote myotube wasting or mitochondrial abnormalities, but we cannot dismiss the possibility that these cells could secrete such factors in vivo within the native tumor microenvironment.