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.