Increased tumour burden alters skeletal muscle properties in the KPC mouse model of pancreatic cancer

Abstract

Background

Cancer cachexia is a multifactorial wasting syndrome that is characterized by the loss of skeletal muscle mass and weakness, which compromises physical function, reduces quality of life, and ultimately can lead to mortality. Experimental models of cancer cachexia have recapitulated this skeletal muscle atrophy and consequent decline in muscle force-generating capacity. We address these issues in a novel transgenic mouse model Kras, Trp53, and Pdx-1-Cre (KPC) of pancreatic ductal adenocarcinoma using multi-parametric magnetic resonance measures.

Methods

KPC mice (n = 10) were divided equally into two groups (n = 5 per group) depending on the size of the tumour, that is, tumour size <250 and >250 mm³. Using multi-parametric magnetic resonance measures, we demonstrated the changes in the gastrocnemius muscle at the microstructural level. In addition, we evaluated skeletal muscle contractile function in KPC mice using an in vivo approach.

Results

Increase in tumour size resulted in decrease in gastrocnemius maximum cross-sectional area, decrease in T₂ relaxation time, increase in magnetization transfer ratio, decrease in mean diffusivity, and decrease in radial diffusivity of water across the muscle fibres. Finally, we detected significant decrease in absolute and specific force production of gastrocnemius muscle with increase in tumour size.

Conclusions

Our findings indicate that increase in tumour size may cause alterations in structural and functional parameters of skeletal muscles and that MR parameters may be used as sensitive biomarkers to non-invasively detect structural changes in cachectic muscles.