Proteomics analysis of C2C12 myotubes treated with atrophy inducing
cancer cell-derived factors
Abstract
Cancer-associated cachexia is a wasting syndrome that results in
dramatic loss of whole-body weight, predominantly due to loss of
skeletal muscle mass. It has been established that cachexia inducing
cancer cells secrete proteins and extracellular vesicles (EVs) that can
induce muscle atrophy. Though several studies examined these cancer-cell
derived factors, targeting some of these components have shown little or
no clinical benefit. To develop new therapies, understanding of the
dysregulated proteins and signalling pathways that regulate catabolic
gene expression during muscle wasting is essential. Here, we sought to
examine the effect of conditioned media (CM) that contain secreted
factors and EVs from cachexia inducing C26 colon cancer cells on C2C12
myotubes using mass spectrometry-based label-free quantitative
proteomics. We identified significant changes in the protein profile of
C2C12 cells upon exposure to C26-derived CM. Functional enrichment
analysis revealed enrichment of proteins associated with inflammation,
mitochondrial dysfunction, muscle catabolism, ROS production, and ER
stress in CM treated myotubes. Furthermore, strong downregulation in
muscle structural integrity and development and/or regenerative pathways
were observed. Together, these enriched proteins in atrophied muscle
could be utilized as potential muscle wasting markers and the
dysregulated biological processes could be employed for therapeutic
benefit in cancer-induced muscle wasting.