Abstract
AIM Cachexia is characterized by losses in lean body mass and
its progression results in worsened quality of life and exacerbated
outcomes in cancer patients. However, the role and impact of fibrosis
during the early stages and development of cachexia in
under-investigated. The purpose of this study was to determine if
fibrosis occurs during cachexia development, and to evaluate this in
both sexes. Methods Female and male C57BL6/J mice were injected
with PBS or Lewis Lung Carcinoma (LLC) at 8‐week of age and tumors were
allowed to develop for 1, 2, 3, or 4 weeks. 3wk and 4wk female
tumor‐bearing mice displayed a dichotomy in tumor growth and were
reassigned to high tumor (HT) and low tumor (LT) groups. In vitro
analyses were also performed on co-cultured C2C12 and 3T3 exposed to LLC
conditioned media. Immunohistochemistry and quantitative PCR analysis
were used to investigate fibrosis and fibrosis related signaling in
skeletal muscle. Results Collagen deposition in skeletal muscle
was increased in the 1wk, LT and HT groups in female mice. However,
collagen deposition was only increased in the 4wk group in male mice. In
general female mice displayed earlier alterations in ECM related genes
beginning at 1 wk post-LLC injection. Whereas this was not seen in
males. Conclusions While overall tumor burden is tightly
correlated to cachexia development in both sexes, fibrotic development
is not. Male mice did not exhibit early-stage alterations in ECM related
genes contrary to what was noted in female mice.