Reprogramming of cancer-associated fibroblasts by apoptotic cancer cells inhibits lung metastasis via Notch1-WISP-1 signaling
作者机构：Department of PhysiologyCollege of MedicineEwha Womans UniversitySeoul07804Korea Inflammation-Cancer Microenvironment Research CenterCollege of MedicineEwha Womans UniversitySeoul07804Korea Department of Molecular MedicineCollege of MedicineEwha Womans UniversitySeoul07804Korea
出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)
年 卷 期：2022年第19卷第12期
页 面：1373-1391页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
主 题：CAFs Apoptotic lung cancer cells Notch1 WiSP-1 Efferocytosis Migration Invasion Metastasis
摘 要：The interplay between apoptotic cancer cells and the tumor microenvironment modulates cancer progression and ***-associated fibroblasts(CAFs)play a crucial role in promoting these events through paracrine ***,we demonstrate that conditioned medium(CM)from lung CAFs exposed to apoptotic cancer cells suppresses TGF-β1-induced migration and invasion of cancer cells and *** exposure of CAFs to apoptotic 344SQ cells(ApoSQ)inhibited CAF migration and invasion and the expression of CAF activation *** secretion of Wnt‐induced signaling protein 1(WISP-1)by CAFs exposed to ApoSQ was required for these antimigratory and anti-invasive *** inhibition of Notch1 activation or siRNA-mediated Notch1 silencing prevented WISP-1 production by CAFs and reversed the antimigratory and anti-invasive *** expression of the Notch ligand delta-like protein 1 on the surface of ultraviolet-irradiated apoptotic lung cancer cells triggered Notch1-WISP-1 *** receptor brain-specific angiogenesis inhibitor 1(BAI1)-Rac1 signaling,which facilitated efferocytosis by CAFs,participated in crosstalk with Notch1 signaling for optimal production of *** addition,a single injection of ApoSQ enhanced WISP-1 production,suppressed the expression of CAF activation markers in isolated Thy1^(+)CAFs,and inhibited lung metastasis in syngeneic immunocompetent mice via Notch1 *** with CM from CAFs exposed to ApoSQ suppressed tumor growth and lung metastasis,whereas treatment with WISP-1-immunodepleted CM from CAFs exposed to ApoSQ reversed the antitumorigenic and antimetastatic ***,treatment with CM from CAFs exposed to apoptotic lung cancer cells could be therapeutically applied to suppress CAF activation,thereby preventing cancer progression and metastasis.
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