The systemic activin response to pancreatic cancer: implications for effective cancer cachexia therapy.

ABSTRACT:

Background

Pancreatic ductal adenocarcinoma (PDAC) is a particularly lethal malignancy partly due to frequent, severe cachexia. Serum activin correlates with cachexia and mortality, while exogenous activin causes cachexia in mice.

Methods

Isoform-specific activin expression and activities were queried in human and murine tumours and PDAC models. Activin inhibition was by administration of soluble activin type IIB receptor (ACVR2B/Fc) and by use of skeletal muscle specific dominant negative ACVR2B expressing transgenic mice. Feed-forward activin expression and muscle wasting activity were tested in vivo and in vitro on myotubes.

Results

Murine PDAC tumour-derived cell lines expressed activin-βA but not activin-βB. Cachexia severity increased with activin expression. Or

SUBMITTER: Zhong X 

PROVIDER: S-EPMC6818463 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature