47 research outputs found
Stromal integrin α11 regulates PDGFRβ signaling and promotes breast cancer progression
Cancer-associated fibroblasts (CAFs) are key actors in modulating the progression of many solid tumors, such as breast cancer (BC). Herein, we identify an integrin alpha 11/PDGFR beta-positive CAF subset displaying tumor-promoting features in BC. In the preclinical MMTV-PyMT mouse model, integrin alpha 11 deficiency led to a drastic reduction of tumor progression and metastasis. A clear association between integrin alpha 11 and PDGFR beta was found at both transcriptional and histological levels in BC specimens. High stromal integrin alpha 11/PDGFR beta expression was associated with high grades and poorer clinical outcome in human BC patients. Functional assays using 5 CAF subpopulations (1 murine, 4 human) revealed that integrin alpha 11 promotes CAF invasion and CAF-induced tumor cell invasion upon PDGF-BB stimulation. Mechanistically, the proinvasive activity of integrin alpha 11 relies on its ability to interact with PDGFR beta in a ligand-dependent manner and to promote its downstream JNK activation, leading to the production of tenascin C, a proinvasive matricellular protein. Pharmacological inhibition of PDGFR beta and JNK impaired tumor cell invasion induced by integrin alpha 11 CAFs. Collectively, our study uncovers an integrin alpha 11 subset of protumoral CAFs that exploits the PDGFR beta/JNK signaling axis to promote tumor invasiveness in BC
IsCAM: Metabolism and Microenvironment in Cancer Plasticity: 2nd Annual Meeting of the International Society of Cancer Metabolism
info:eu-repo/semantics/publishe
Cancer associated fibroblast‐derived integrin a11 regulates PDGFRb signaling to promote breast cancer progression
Studio dell'attività antivascolare dei derivati antimitotici
L'attività antivascolare di alcuni derivati della Combretastatina è stata valutata tramite lo scratch test, la morfogenesi su Matrigel, vascular permeability essay, tecniche di immunofluorescenza e Western Blotting. La loro attività antiproliferativa è stata testata sia su linee cellulari tumorali che non tumoral
Cancer associated fibroblast‐derived integrin a11 regulates PDGFRb signaling to promote breast cancer progression
EMBL-EMBL Symposium: Tumour Microenvironment and Signalling
info:eu-repo/semantics/publishe