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Download fileReshaping Prostate Tumor Microenvironment To Suppress Metastasis via Cancer-Associated Fibroblast Inactivation with Peptide-Assembly-Based Nanosystem
journal contribution
posted on 30.09.2019, 15:35 authored by Jiayan Lang, Xiao Zhao, Yingqiu Qi, Yinlong Zhang, Xuexiang Han, Yanping Ding, Jiajing Guan, Tianjiao Ji, Ying Zhao, Guangjun NieProstate
cancer is one of the most common malignant tumors in men,
and inhibiting metastasis is a key event but still a major challenge
in prostate cancer treatment. Cancer-associated fibroblasts (CAFs)
play an important role in prostate tumor metastasis by shaping the
malignant tumor microenvironment. Herein, we constructed a CAF-targeting
siRNA delivery system by loading the fibroblast activation protein-α
(FAP-α) antibody onto the cell-penetrating peptide (CPP)-based
nanoparticles, which specifically downregulated C–X–C
motif chemokine ligand 12 (CXCL12) expression in CAFs. This regulation
generated a series of changes through inactivating CAFs so that the
malignant prostate tumor microenvironment was reshaped. The tumor
cell invasion, migration, and tumor angiogenesis were significantly
inhibited, which all contributed to the suppression of the metastasis
of an orthotopic prostate tumor. This tumor microenvironment reshaping
strategy via CAF targeting and inactivation provides
an alternative approach for malignant prostate tumor metastasis inhibition.
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Keywords
CPPCancer-Associated Fibroblast Inactivationtumor cell invasiontumor microenvironmentprostate tumor metastasis inhibitionorthotopic prostate tumorCXCLfibroblast activation protein -αprostate tumor microenvironmentPeptide-Assembly-Based Nanosystem Prostate cancerFAPProstate Tumor MicroenvironmentCAF-targeting siRNA delivery systemprostate tumor metastasisprostate cancer treatment