Periostin limits tumor response to VEGFA inhibition. - Archive ouverte HAL Access content directly
Journal Articles Cell Reports Year : 2018

Periostin limits tumor response to VEGFA inhibition.

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Abstract

Resistance to antiangiogenic drugs limits their applicability in cancer therapy. Here, we show that revascularization and progression of pancreatic neuroendocrine tumors (PNETs) under extended vascular-endothelial growth factor A (VEGFA) blockade are dependent on periostin (POSTN), a matricellular protein expressed by stromal cells. Genetic deletion of Postn in RIP1-Tag2 mice blunted tumor rebounds of M2-like macrophages and αSMA+ stromal cells in response to prolonged VEGFA inhibition and suppressed PNET revascularization and progression on therapy. POSTN deficiency also impeded the upregulation of basic fibroblast growth factor (FGF2), an adaptive mechanism previously implicated in PNET evasion from antiangiogenic therapy. Higher POSTN expression correlated with markers of M2-like macrophages in human PNETs, and depleting macrophages with a colony-stimulating factor 1 receptor (CSF1R) antibody inhibited PNET revascularization and progression under VEGFA blockade despite continued POSTN production. These findings suggest a role for POSTN in orchestrating resistance to anti-VEGFA therapy in PNETs.
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hal-02185254 , version 1 (28-09-2022)

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Attribution - NonCommercial - NoDerivatives - CC BY 4.0

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Ionna Keklikoglou, Ece Kadioglu, Stefan Bissinger, B Langlois, Axel Bellotti, et al.. Periostin limits tumor response to VEGFA inhibition.. Cell Reports, 2018, 22 (10), pp.2530-2540. ⟨10.1016/j.celrep.2018.02.035⟩. ⟨hal-02185254⟩
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