2026-07-23T17:12:25Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/162892024-11-29T20:54:37Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc González-Muñoz, Teresa author Di Giannatale, Angela author Garcia-Silva, Susana author Santos, Vanesa author Sanchez-Redondo, Sara author Savini, Claudia author Graña-Castro, Osvaldo author Blanco-Aparicio, Carmen author Fischer, Suzanne author De Wever, Olivier author Creus-Bachiller, Edgar author Ortega-Bertran, Sara author Pisapia, David J author Rodríguez-Peralto, José L author Fernández-Rodríguez, Juana author Romagosa, Cleofe author Alaggio, Rita author Benassi, Maria Serena author Pazzaglia, Laura author Scotlandi, Katia author Ratner, Nancy author Yohay, Kaleb author Theuer, Charles P author Peinado Selgas, Hector author 2023-07-11 PURPOSE Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft-tissue sarcomas that lack effective treatments, underscoring the urgent need to uncover novel mediators of MPNST pathogenesis that may serve as potential therapeutic targets. Tumor angiogenesis is considered a critical event in MPNST transformation and progression. Here, we have investigated whether endoglin (ENG), a TGF-β coreceptor with a crucial role in angiogenesis, could be a novel therapeutic target in MPNSTs. EXPERIMENTAL DESIGN ENG expression was evaluated in human peripheral nerve sheath tumor tissues and plasma samples. Effects of tumor cell-specific ENG expression on gene expression, signaling pathway activation and in vivo MPNST growth and metastasis were investigated. The efficacy of ENG targeting in monotherapy or in combination with MEK inhibition was analyzed in xenograft models. RESULTS ENG expression was found to be upregulated in both human MPNST tumor tissues and plasma circulating small extracellular vesicles. We demonstrated that ENG modulates Smad1/5 and MAPK/ERK pathway activation and pro-angiogenic and pro-metastatic gene expression in MPNST cells and plays an active role in tumor growth and metastasis in vivo. Targeting with ENG-neutralizing antibodies (TRC105/M1043) decreased MPNST growth and metastasis in xenograft models by reducing tumor cell proliferation and angiogenesis. Moreover, combination of anti-ENG therapy with MEK inhibition effectively reduced tumor cell growth and angiogenesis. CONCLUSIONS Our data unveil a tumor-promoting function of ENG in MPNSTs and support the use of this protein as a novel biomarker and a promising therapeutic target for this disease. Clin Cancer Res. 2023 ;CCR-22-2462. 10.1158/1078-0432.CCR-22-2462 1557-3265 Clinical cancer research : an official journal of the American Association for Cancer Research 37432984 http://hdl.handle.net/20.500.12105/16289 MPNST angiogenesis metastasis endoglin targeted therapy combination treatment Endoglin, a novel biomarker and therapeutical target to prevent malignant peripheral nerve sheath tumor growth and metastasis.