Suchergebnisse

This study was supported by grants from the Plan Nacional de I+D+I 2013-2016 ISCIII PI16/00280 and CIBERONC (CB16/12/00390), Fundación Merck Salud (17-CC-008), the Instituto de Investigación Sanitariadel 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.

This study was supported by grants from the Plan Nacional de I+D+I 2013-2016 ISCIII (PI16/00280 and PI19/00560) to JMGP), CIBERONC (CB16/12/00390 to JPR), the Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Ayudas a Grupos PCTI Principado de Asturias (IDI2018/155 to JPR), 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, PI16/00280, CIBERONC (CB16/12/00390), and MINECO/FEDER (SAF2016-75286-R), 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.

This study was supported by grants from the Plan Nacional de I+D+I 2013–2016 [ISCIII (PI16/00280 to JMGP and CPII16/00049 to RR), CIBERONC (CB16/12/00390 to JPR and CB16/12/00443 to LMM) and MINECO (SAF2016-75286-R to RR)], the Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Fundación Merck Salud (17-CC-008 to JPR), Ayudas a Grupos PCTI Principado de Asturias (IDI2018/155 to JPR) and the FEDER Funding Program from the European Union.

This study was supported by grants from the Plan Nacional de I+D+I 2013-2016 [ISCIII (CP13/00013, PI13/00259 and PI16/00280 to JMGP and CPII16/00049 to RR), Red Temática de Investigación Cooperativa en Cáncer (RTICC) (RD12/0036/0015), CIBERONC (CB16/12/00390 to JPR and CB16/12/00443 to LM) and MINECO (SAF2013-42946-R and SAF2016-75286-R to RR)], the Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), the Plan de Ciencia Tecnología e Innovación del Principado de Asturias (GRUPIN14-003 to JPR), Fundación Merck Salud (17-CC-008 to JPR), and the FEDER Funding Program from the European Union.