3 research outputs found
GARP promotes the proliferation and therapeutic resistance of bone sarcoma cancer cells through the activation of TGF-β
Sarcomas are mesenchymal cancers with poor prognosis, representing about 20% of all solid malignancies in children,
adolescents, and young adults. Radio- and chemoresistance are common features of sarcomas warranting the search
for novel prognostic and predictive markers. GARP/LRRC32 is a TGF-β-activating protein that promotes immune
escape and dissemination in various cancers. However, if GARP affects the tumorigenicity and treatment resistance of
sarcomas is not known. We show that GARP is expressed by human osteo-, chondro-, and undifferentiated
pleomorphic sarcomas and is associated with a significantly worse clinical prognosis. Silencing of GARP in bone
sarcoma cell lines blocked their proliferation and induced apoptosis. In contrast, overexpression of GARP promoted
their growth in vitro and in vivo and increased their resistance to DNA damage and cell death induced by etoposide,
doxorubicin, and irradiation. Our data suggest that GARP could serve as a marker with therapeutic, prognostic, and
predictive value in sarcoma. We propose that targeting GARP in bone sarcomas could reduce tumour burden while
simultaneously improving the efficacy of chemo- and radiotherapy.Instituto de Salud Carlos IIIEuropean Union (EU)
PI15/00794
PI18/00826
CPII15/00032
PI15/02015Junta de Andalucía
C-0013-2018Spanish Government
PEJ-2014-A-46314Agencia Estatal de Investigación (AEI) [MICINN/Fondo Europeo de Desarrollo Regional (FEDER)]
SAF-2016-75286-RISCIII/FEDER [Miguel Servet Program]
CPII16/00049ISCIII/FEDER [Sara Borrell Program]
CD16/00103Servicio de Salud del Principado de Asturias, Instituto de Salud Carlos III
PT17/0015/0023Fundación Bancaria Cajastur
PT17/0015/0023ISCIII/FEDER [Consorcio CIBERONC]
CB16/12/0039