RT Journal Article
T1 GARP promotes the proliferation and therapeutic resistance of bone sarcoma cancer cells through the activation of TGF-β.
A1 Carrillo-Galvez, Ana Belen
A1 Quintero, Juan Esteban
A1 Rodríguez, Rene
A1 Menéndez, Sofia T
A1 Victoria Gonzalez, M
A1 Blanco-Lorenzo, Veronica
A1 Allonca, Eva
A1 de Araujo Farias, Virginea
A1 Gonzalez-Correa, Juan Elias
A1 Erill-Sagales, Nadina
A1 Martinez-Zubiaurre, Iñigo
A1 Hellevik, Turid
A1 Sanchez-Hernandez, Sabina
A1 Muñoz, Pilar
A1 Zurita, Federico
A1 Martin, Francisco
A1 Rodriguez-Manzaneque, Juan Carlos
A1 Anderson, Per
K1 Adolescent
K1 Adult
K1 Aged
K1 Aged, 80 and over
K1 Animals
K1 Bone Neoplasms
K1 Cell Line, Tumor
AB 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.
PB Nature Publishing Group
YR 2020
FD 2020-10-27
LK http://hdl.handle.net/10668/16626
UL http://hdl.handle.net/10668/16626
LA en
NO Carrillo-Gálvez AB, Quintero JE, Rodríguez R, Menéndez ST, Victoria González M, Blanco-Lorenzo V, et al.  GARP promotes the proliferation and therapeutic resistance of bone sarcoma cancer cells through the activation of TGF-β. Cell Death Dis. 2020 Nov 17;11(11):985.
NO This work has been financed by the Instituto de Salud Carlos III, Spain (www.isciii.es) and Fondo Europeo de Desarrollo Regional (FEDER), from the European Union, through the research grants PI15/00794, PI18/00826, CPII15/00032 (P.A.), and PI15/02015 (F.M.). P.A. is supported by the Consejería de Salud, Junta de Andalucía through the contract “Nicolás Monardes” (C-0013-2018). A. B. C-G. was supported by the Ministerio de Ciencia y Tecnología, through the contract PEJ-2014-A-46314. This work was also supported by the Agencia Estatal de Investigación (AEI) [MICINN/Fondo Europeo de Desarrollo Regional (FEDER) (SAF-2016-75286-R to R.R.), ISCIII/FEDER [Miguel Servet Program (CPII16/00049 to R.R.), Sara Borrell Program (CD16/00103 to S-T.M.) and Consorcio CIBERONC (CB16/12/00390)]. The authors acknowledge the use of the Data from the Cancer Cell Line Encyclopedia (CCLE) database by the Broad Institute (www.broadinstitute.org/ccle). We declare that those who carried out the original analysis and collection of the data bear no responsibility for the further analysis or interpretation of it. The BM-MSCs were kindly provided by Jose M. Moraleda and Ana Mª García Hernández (Unidad de Terapia Celular y Trasplante Hematopoyético, Servicio Hematología, Hospital Virgen de la Arrixaca, Murcia, Spain). For its collaboration, we want to acknowledge the Principado de Asturias BioBank (PT17/0015/0023), financed jointly by Servicio de Salud del Principado de Asturias, Instituto de Salud Carlos III and Fundación Bancaria Cajastur and integrated in the Spanish National Biobank Network. We also want to thank Oscar Estupiñan and Verónica Rey (Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain) for their contribution to the derivation and culture of primary cell lines.
DS RISalud
RD Apr 9, 2025