ACVR2B antagonism as a countermeasure to multi-organ perturbations in metastatic colorectal cancer cachexia.

Journal of Cachexia, Sarcopenia and Muscle
Joshua R HuotAndrea Bonetto

Abstract

Advanced colorectal cancer (CRC) is often accompanied by the development of liver metastases, as well as cachexia, a multi-organ co-morbidity primarily affecting skeletal (SKM) and cardiac muscles. Activin receptor type 2B (ACVR2B) signalling is known to cause SKM wasting, and its inhibition restores SKM mass and prolongs survival in cancer. Using a recently generated mouse model, here we tested whether ACVR2B blockade could preserve multiple organs, including skeletal and cardiac muscle, in the presence of metastatic CRC. NSG male mice (8 weeks old) were injected intrasplenically with HCT116 human CRC cells (mHCT116), while sham-operated animals received saline (n = 5-10 per group). Sham and tumour-bearing mice received weekly injections of ACVR2B/Fc, a synthetic peptide inhibitor of ACVR2B. mHCT116 hosts displayed losses in fat mass ( - 79%, P < 0.0001), bone mass ( - 39%, P < 0.05), and SKM mass (quadriceps: - 22%, P < 0.001), in line with reduced muscle cross-sectional area ( - 24%, P < 0.01) and plantarflexion force ( - 28%, P < 0.05). Further, despite only moderately affected heart size, cardiac function was significantly impaired (ejection fraction %: - 16%, P < 0.0001; fractional shortening %: - 25%, P < 0.0001) in the ...Continue Reading

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Citations

Feb 6, 2021·International Journal of Molecular Sciences·Joshua R HuotAndrea Bonetto
Apr 27, 2021·Experimental Biology and Medicine·Fabrizio PinAndrea Bonetto
Jul 8, 2021·Cancer Letters·Fabrizio PinLynda F Bonewald

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Datasets Mentioned

BETA
GSE149604

Methods Mentioned

BETA
xenograft
protein assay
Infrared Imaging
Assay
PCR
ubiquitination

Clinical Trials Mentioned

NCT01433263
NCT01505530
NCT02631070
NCT03496207

Software Mentioned

SkyScan
DAVID
CTAn
Partek® Flow®
MultiQC
ImageJ
FastQC
GraphPad Prism
STAR RNA seq aligner
featureCounts

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