ISCOMS 2025 SCIENCE BEYOND BORDERS
112

Muscle atrophy in lung cancer cachexia: towards a 
living, single-fiber approach

Carolina Palacios-Montoya
Colombia
University of Antioquia
Co-authors: Mr. Andres F Milan, Dr Marco A Giraldo, Dr Geysson J Fernandez, Dr Robson F Carvalho, Dr Juan C 
Calderon

Introduction
Cancer is a major public health challenge because of its high prevalence, morbidity, mortality, and health-
care costs. Among its systemic complications, cancer-induced cachexia (CC) is particularly debilitating, fur-
ther hindering cancer treatments and predicting poor prognosis (WHO, 2019; Fearon et al. 2011; Lim et al. 
2020). Despite this, the CC pathophysiology remains poorly understood at the muscle cellular level. Here, we 
develop a single-muscle fiber murine model with potential to address CC cellular mechanisms.

Materials & Methods
One million Lewis Lung Carcinoma (LLC1, ATCC-CRL: 1642) cells (passage 4) were injected into Tumor-Bear-
ing (TB) C57BL/6 adult mice (3 males, 3 females). Controls (2 males, 2 females) received phosphate buffered 
saline. Body weight, temperature, thigh and calf circumferences, and tumor diameter were repeatedly meas-
ured. After 241.8 days, mice (10.350.25 weeks old) were sacrificed. Tumors, liver, heart, spleen, fat depots 
(retroperitoneal, visceral, epididymal), and muscles (Flexor Digitorum Brevis (FDB), Peroneus Longus (PL), 
Extensor Digitorum Longus (EDL), Plantaris, Soleus) were dissected and weighed. Muscles were dissociated 
in collagenase type II; only isolated, well-contracting fibers were imaged and morphometric analyses were 
performed using ImageJ.

Results
Control animals gained 2.390.54 g but TB mice lost 1.151.6 g (p=0.006). Thigh and calf circumferences tend-
ed to decrease, but spleens were significantly heavier in TB mice (162.677.16 mg) compared to controls 
(57.3510.01 mg; p=0.037). The greatest difference in fat tissue was observed in the visceral depot (mg): con-
trol 329.85117.19, TB 233.62105.70, though not significant (p=0.318). Regarding muscle tissue weight, the 
greatest change was observed in the EDL (mg): control 9.531.45, TB 8.071.24 (p=0.190). The FDB, EDL and PL 
fibers of TB mice showed a 20.810.5% (p=0.01) lower diameter (n=199) than the control ones (n=111). The 
Soleus fibers remained unaffected (p=0.521)

Conclusion
The decreases in weights and circumferences, as well as the splenomegaly, confirm the development of in-
flammation and CC in the TB mice. This study offers the first evidence of muscle atrophy at the single-fiber 
level in a CC murine model, paving the way for future detailed physiological, biophysical, molecular and 
mathematical studies of living single skeletal muscle fibers in the context of CC (CODI 2021-40170; FUA-001-
2024/2025-0072).