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Removing the hedgehog signal that builds the scar tissue around pancreatic tumours in mice gave less stroma but more aggressive, more vascular cancers, and only anti-angiogenic treatment helped them.
Sonic hedgehog, overexpressed by neoplastic cells and driving a fibroblast-rich desmoplastic stroma, was deleted in a mouse model of pancreatic ductal adenocarcinoma. Shh-deficient tumours had reduced stromal content but were more aggressive, undifferentiated, more vascular and more proliferative, effects fully recapitulated by a smoothened inhibitor in control mice. VEGFR blockade selectively improved survival of Shh-deficient tumours, indicating that hedgehog-driven stroma suppresses tumour growth partly by restraining angiogenesis.
Published alongside Ozdemir, it explains why the hedgehog inhibitor trials in patients failed and why stromal targets are now chosen for their signalling rather than their bulk.
Shares Hedgehog signalling, Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Pancreatic ductal adenocarcinoma.
Shares Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Pancreatic ductal adenocarcinoma.
Shares Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Pancreatic ductal adenocarcinoma.
Shares Cancer Cell, Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Pancreatic ductal adenocarcinoma.
Shares Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Pancreatic ductal adenocarcinoma.
Shares Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Pancreatic ductal adenocarcinoma.
Shares Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Pancreatic ductal adenocarcinoma.
Shares Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Pancreatic ductal adenocarcinoma.