Significance
statement
Cachexia is the immediate cause of death for 20-40% of cancer patients.
Cachexia is characterized by tissue fibrosis. The impact of cachexia
progression on skeletal muscle fibrosis is unknown. Additionally, how
sex alters the cachexia-associated fibrotic response in skeletal muscle
is unknown. The principal finding of this study was that while tumor
burden is tightly correlated to cachexia progression in both sexes,
fibrotic development was not. Females demonstrated mild collagen
deposition early whereas males did not demonstrate collagen deposition
until much later with a much more exaggerated response. The lack of SMAD
2 and 3 induction suggests a non-canonical signaling pathway is involved
in ECM regulation during the progression of cachexia.