Results
Confirmation of Cachexia
Development.
Female and male body weight, tumor weight, hindlimb skeletal muscle
weight, and organ weights of PBS and LLC-injected C57BL/6J mice were
reported previously by Lim et. al. 27 and Brown et.
al. 28, 29, respectively. Neither male nor female mice
saw significant reductions in tumor-free body weight compared to PBS
control. In the male, the HT group showed lower muscle and fat mass
compared to PBS control. In female mice, the 4 wk group showed lower
muscle and fat mass compared to PBS control. Additionally, in females,
the LT and HT groups as well as the 3 wk and 4 wk groups in males showed
splenomegaly compared to PBS control.
Excessive Deposition of Collagen in
Skeletal
Muscle
Picrosirius Red staining—a marker of collagen deposition—within the
plantaris (female) and TA (male) muscle was performed to determine
overall fibrosis during the development of cancer cachexia. 1wk and LT
and HT female mice saw an ~2-fold greater
(p<0.05) collagen deposition compared to the PBS and 2wk
groups (Figure 1A). Male mice saw no significant differences in collagen
deposition until 4 weeks post-LLC injection where there was an
~3-fold greater (p<0.05) deposition compared
to all other groups (Figure 1B).
Collagen mRNA Abundance is Altered
during Cancer Cachexia
Development
In female mice, collagen 1 and 3 mRNA abundance were ~
2.8 and ~1.7-fold greater in the 1 wk post-LLC injection
group compared to all other groups, respectively (p<0.05;
Figure 2A & 2B), however the ratio of Collagen 3:1 mRNA abundance was
~ 78% lower in 1wk post-LLC injection female mice
compared to PBS (p<0.05; Figure 2C). In male mice, the 2 wk
post-LLC injection group had an ~ 2.2-fold and 2.8-fold
higher collagen 1 mRNA abundance compared to the PBS group and 4 wk
post-LLC injection groups, respectively (p<0.05; Figure 2D).
In male mice, the 3 and 4 wk post-LLC injection groups had
~56% lower collagen 3 mRNA abundance compared to the 1
wk post-LLC injection group (p<0.05; Figure 2E). In male mice,
the ratio of collagen 3:1 was ~113% higher in the 4 wk
post-LLC group compared to the 1, 2, and 3 wk post-LLC injection groups
(p<0.05; Figure 2F).