GARP promotes the proliferation and therapeutic resistance of bone sarcoma cancer cells through the activation of TGF-β
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Carrillo Gálvez, Ana Belén; Esteban Quintero, Juan; González Correa, Juan Elías; Sánchez Hernández, Sabina; Muñoz Rivas, María Pilar; Zurita Martínez, Federico; Martín, Francisco; Rodríguez Manzaneque, Juan Carlos; Anderson, Per OlofEditorial
Springer Nature
Date
2020-11-17Referencia bibliográfica
Carrillo-Gálvez, A. B., Quintero, J. E., Rodríguez, R., Menéndez, S. T., González, M. V., Blanco-Lorenzo, V., ... & Anderson, P. (2020). GARP promotes the proliferation and therapeutic resistance of bone sarcoma cancer cells through the activation of TGF-β. Cell death & disease, 11(11), 1-12. [DOI: 10.1038/s41419-020-03197-z]
Sponsorship
Instituto de Salud Carlos III; European Union (EU) PI15/00794 PI18/00826 CPII15/00032 PI15/02015; Junta de Andalucía C-0013-2018; Spanish Government PEJ-2014-A-46314; Agencia Estatal de Investigación (AEI) [MICINN/Fondo Europeo de Desarrollo Regional (FEDER)] SAF-2016-75286-R; ISCIII/FEDER [Miguel Servet Program] CPII16/00049; ISCIII/FEDER [Sara Borrell Program] CD16/00103; Servicio de Salud del Principado de Asturias, Instituto de Salud Carlos III PT17/0015/0023; Fundación Bancaria Cajastur PT17/0015/0023; ISCIII/FEDER [Consorcio CIBERONC] CB16/12/00390Abstract
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.