Suchergebnisse

This study was supported by grants from the Plan Nacional de I+D+I 2013-2016 ISCIII (PI13/00259), PI16/00280, and CIBERONC (CB16/12/00390) Spain, the Principado de Asturias (GRUPIN14-003), Fundación Merck Salud (17-CC-008), the Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), and the FEDER Funding Program from the European Union. SAT and MAV were recipients of fellowships from ISCIII (FI12/00415 and CD13/00157, respectively). ; Álvarez-Teijeiro, S., García-Inclán, C., Villaronga, M.Á., Casado, P., Hermida-Prado, F., Granda-Díaz, R., Rodrigo, J.P., Calvo, F., Del-Río-ibisate, N., Gandarillas, A., Morís, F., Hermsen, M., Cutillas, P., García-Pedrero, J.M.

Plan Nacional de I+D+I Instituto de Salud Carlos III [PI11/00929]; Plan Nacional de I+D+I ISCIII [CP13/00013, PI13/00259]; Red Tematica de Investigacion Cooperativa en Cancer (RTICC), Spain [RD12/0036/0015]; Fundacion Bancaria Caja de Ahorros de Asturias-IUOPA; FEDER Funding Program from the European Union; ISCIII [CD13/00157]; PFIS ISCIII [FI12/00415]

This study was supported by grants from the Plan Nacional de I+D+I 2013-2016 ISCIII (PI13/00259), RD12/0036/0015 of Red Temática de Investigación Cooperativa en Cáncer (RTICC), PI16/00280 and CIBERONC (CB16/12/00390 and CB16/12/00228), the Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), PCTI-Asturias (GRUPIN14-003), Fundación Bancaria Caja de Ahorros de Asturias-IUOPA and the FEDER Funding Program from the European Union.

© 2018 by the authors. ; This study investigates for the first time the crosstalk between stromal fibroblasts and cancer stem cell (CSC) biology in head and neck squamous cell carcinomas (HNSCC), with the ultimate goal of identifying effective therapeutic targets. The effects of conditioned media from cancer-associated fibroblasts (CAFs) and normal fibroblasts (NFs) on the CSC phenotype were assessed by combining functional and expression analyses in HNSCC-derived cell lines. Further characterization of CAFs and NFs secretomes by mass spectrometry was followed by pharmacologic target inhibition. We demonstrate that factors secreted by CAFs but not NFs, in the absence of serum/supplements, robustly increased anchorage-independent growth, tumorsphere formation, and CSC-marker expression. Modulators of epidermal growth factor receptor (EGFR), insulin-like growth factor receptor (IGFR), and platelet-derived growth factor receptor (PDGFR) activity were identified as paracrine cytokines/factors differentially secreted between CAFs and NFs, in a mass spectrometry analysis. Furthermore, pharmacologic inhibition of EGFR, IGFR, and PDGFR significantly reduced CAF-induced tumorsphere formation and anchorage-independent growth suggesting a role of these receptor tyrosine kinases in sustaining the CSC phenotype. These findings provide novel insights into tumor stroma–CSC communication, and potential therapeutic targets to effectively block the CAF-enhanced CSC niche signaling circuit. ; This study was supported by grants from the Plan Nacional de I+D+I 2013-2016 ISCIII (PI13/00259), PI16/00280, and CIBERONC (CB16/12/00390) Spain, the Principado de Asturias (GRUPIN14-003), Fundación Merck Salud (17-CC-008), the Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), and the FEDER Funding Program from the European Union. SAT and MAV were recipients of fellowships from ISCIII (FI12/00415 and CD13/00157, respectively).

Plan Nacional de I + D + I ISCIII [CP13/00013, PI13/00259]; Red Tematica de Investigacion Cooperativa en Cancer (RTICC) [RD12/0036/0015]; CIBERONC Spain [CB16/12/00390]; Principado de Asturias [V-PA-13-ECOEMP-69, GRUPIN14-097]; FEDER Funding Program from the European Union; ISCIII [FI12/00415, CD13/00157]; [PI16/00280]

This study was supported by grants from the Plan Nacional de I+D+I 2013-2016 ISCIII (PI13/00259), RD12/0036/0015 of Red Temática de Investigación Cooperativa en Cáncer (RTICC), PI16/00280, and CIBERONC(CB16/12/00390 and CB16/12/00401), CIBER-BBN (CB06/01/1031) Spain, Fundación Merck Salud (17-CC-008), the Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), PCTI-Asturias (GRUPIN14-003), Fundación Bancaria Caja de Ahorros de Asturias-IUOPA, and the FEDER Funding Program from the European Union. STM (Sara Borrell Program-CD16/00103) and RR (Miguel Servet II Program-CPII16/00049) were recipients of fellowships from ISCIII.We thank the samples and technical assistance kindly provided by the Principado de Asturias BioBank (PT13/0010/0046), 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 Biobanks Network, and IIB Sant Pau. ; Hermida-Prado, Francisco J., Tirados Menendez, Sofia, Albornoz-Afanasiev, Pablo, Granda-Diaz, Rocio, Alvarez-Teijeiro, Saul, Angeles Villaronga, M., Allonca, Eva, Alonso-Duran, Laura, Leon, Xavier, Alemany, Laia, Mena, Marisa, del-Rio-Ibisate, Nagore, Astudillo, Aurora, Rodriguez, Rene, Rodrigo, Juan P., Garcia-Pedrero, Juana M.

This study was supported by grants from the Plan Nacional de I+D+I 2008–2011 Instituto de Salud Carlos III (PI11/00929 to JPR and CS) and Plan Nacional de I+D+I 2013–2016 ISCIII (CP13/00013 and PI13/00259 to JMGP), RD12/0036/0015 of Red Temática de Investigación Cooperativa en Cáncer (RTICC), Spain, and the FEDER Funding Program from the European Union. S.A.T. and M.A.V. are recipients of a fellowship from ISCIII (FI12/00415 and CD13/00157, respectively).

This study was supported by grants from the Plan Nacional de I+D+I 2008-2011 Instituto de Salud Carlos III (PI11/00929 to JPR) and Plan Nacional de I+D+I 2013-2016 ISCIII (CP13/00013 and PI13/00259 to JMGP),RD12/0036/0015 of Red Temática de Investigación Cooperativa en Cáncer (RTICC), Spain, and the FEDER Funding Program from the European Union. M.A.V. is recipient of a fellowship from ISCIII (CD13/00157). Work in the laboratory of G.S. was funded by grant NIH R01CA109525 ; García-Carracedo, D., Ángeles Villaronga, M., Álvarez-Teijeiro, S., Hermida-Prado, F., Santamaría, I., Allonca, E., Suárez-Fernández, L., Victoria Gonzalez, M., Milagros Balbín, M., Astudillo, A., Martínez-Camblor, P., Su, G.H., Rodrigo, J.P., García-Pedrero, J.M.