PMID- 36004775 OWN - NLM STAT- MEDLINE DCOM- 20221027 LR - 20221027 IS - 1521-4095 (Electronic) IS - 0935-9648 (Linking) VI - 34 IP - 43 DP - 2022 Oct TI - Transformable ECM Deprivation System Effectively Suppresses Renal Cell Carcinoma by Reversing Anoikis Resistance and Increasing Chemotherapy Sensitivity. PG - e2203518 LID - 10.1002/adma.202203518 [doi] AB - Extracellular matrix (ECM) is crucial in various biological functions during tumor progression, including induction of anoikis resistance and cell adhesion-mediated drug resistance (CAM-DR). Fibronectin (FN) is a vital ECM component with direct regulatory effects on ECM-mediated anoikis resistance and CAM-DR, making it an attractive and innovative therapeutic target for depriving ECM in tumor tissue. Herein, an ECM deprivation system (EDS) is developed based on FN targeting self-assembly peptide for constructing nanofibers in the ECM of renal cell carcinoma (RCC), which contributes to: i) targeting and recognizing FN to form nanofibers for long-term retention in ECM, ii) reversing anoikis resistance via arresting the FN signaling pathway, and iii) serving as a drug-loading platform for sensitizing chemotherapy by ameliorating CAM-DR. The results reveal that EDS significantly reverses anoikis resistance of RCC cells by inhibiting the phosphorylation of FAK, a positive regulator of the FN signaling pathway. Meanwhile, EDS serves as a chemotherapy-sensitizer of cancer, exerting significant synergistic effects with doxorubicin (DOX). In vivo validation experiments show that EDS effectively suppresses metastasis and tumor growth with chemotherapy resistance. Collectively, the innovative EDS notably inhibits the tumor-promoting effect of ECM and may provide a novel approach for suppressing ECM and enhancing chemo-drug sensitivity. CI - (c) 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH. FAU - Wang, Lu AU - Wang L AD - NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, 150001, China. AD - Department of Urology, The Fourth Hospital of Harbin Medical University, Heilongjiang Key Laboratory of Scientific Research in Urology, No. 37 Yi-Yuan Street, Nangang District, Heilongjiang Province, Harbin, 150001, China. FAU - Li, Cong AU - Li C AD - NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, 150001, China. AD - Department of Urology, The Fourth Hospital of Harbin Medical University, Heilongjiang Key Laboratory of Scientific Research in Urology, No. 37 Yi-Yuan Street, Nangang District, Heilongjiang Province, Harbin, 150001, China. FAU - Wang, Jiaqi AU - Wang J AD - NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, 150001, China. AD - Department of Urology, The Fourth Hospital of Harbin Medical University, Heilongjiang Key Laboratory of Scientific Research in Urology, No. 37 Yi-Yuan Street, Nangang District, Heilongjiang Province, Harbin, 150001, China. FAU - Yang, Guang AU - Yang G AD - Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China. FAU - Lv, Yulin AU - Lv Y AD - NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, 150001, China. AD - Department of Urology, The Fourth Hospital of Harbin Medical University, Heilongjiang Key Laboratory of Scientific Research in Urology, No. 37 Yi-Yuan Street, Nangang District, Heilongjiang Province, Harbin, 150001, China. FAU - Fu, Bo AU - Fu B AD - NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, 150001, China. AD - Department of Urology, The Fourth Hospital of Harbin Medical University, Heilongjiang Key Laboratory of Scientific Research in Urology, No. 37 Yi-Yuan Street, Nangang District, Heilongjiang Province, Harbin, 150001, China. FAU - Jian, Lingrui AU - Jian L AD - NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, 150001, China. AD - Department of Urology, The Fourth Hospital of Harbin Medical University, Heilongjiang Key Laboratory of Scientific Research in Urology, No. 37 Yi-Yuan Street, Nangang District, Heilongjiang Province, Harbin, 150001, China. FAU - Ma, Jinpeng AU - Ma J AD - NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, 150001, China. AD - Department of Urology, The Fourth Hospital of Harbin Medical University, Heilongjiang Key Laboratory of Scientific Research in Urology, No. 37 Yi-Yuan Street, Nangang District, Heilongjiang Province, Harbin, 150001, China. FAU - Yu, Jiaao AU - Yu J AD - NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, 150001, China. AD - Department of Urology, The Fourth Hospital of Harbin Medical University, Heilongjiang Key Laboratory of Scientific Research in Urology, No. 37 Yi-Yuan Street, Nangang District, Heilongjiang Province, Harbin, 150001, China. FAU - Yang, Zongzheng AU - Yang Z AD - NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, 150001, China. AD - Department of Urology, The Fourth Hospital of Harbin Medical University, Heilongjiang Key Laboratory of Scientific Research in Urology, No. 37 Yi-Yuan Street, Nangang District, Heilongjiang Province, Harbin, 150001, China. FAU - Wu, Peng AU - Wu P AD - NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, 150001, China. AD - Department of Urology, The Fourth Hospital of Harbin Medical University, Heilongjiang Key Laboratory of Scientific Research in Urology, No. 37 Yi-Yuan Street, Nangang District, Heilongjiang Province, Harbin, 150001, China. FAU - Li, Guangbin AU - Li G AD - NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, 150001, China. AD - Department of Urology, The Fourth Hospital of Harbin Medical University, Heilongjiang Key Laboratory of Scientific Research in Urology, No. 37 Yi-Yuan Street, Nangang District, Heilongjiang Province, Harbin, 150001, China. FAU - Liu, Xiao AU - Liu X AD - NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, 150001, China. AD - Department of Urology, The Fourth Hospital of Harbin Medical University, Heilongjiang Key Laboratory of Scientific Research in Urology, No. 37 Yi-Yuan Street, Nangang District, Heilongjiang Province, Harbin, 150001, China. FAU - Kang, Zhijian AU - Kang Z AD - NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, 150001, China. AD - Department of Urology, The Fourth Hospital of Harbin Medical University, Heilongjiang Key Laboratory of Scientific Research in Urology, No. 37 Yi-Yuan Street, Nangang District, Heilongjiang Province, Harbin, 150001, China. FAU - Wang, Ziqi AU - Wang Z AD - NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, 150001, China. AD - Department of Urology, The Fourth Hospital of Harbin Medical University, Heilongjiang Key Laboratory of Scientific Research in Urology, No. 37 Yi-Yuan Street, Nangang District, Heilongjiang Province, Harbin, 150001, China. FAU - Wang, Lei AU - Wang L AD - NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, 150001, China. AD - Department of Urology, The Fourth Hospital of Harbin Medical University, Heilongjiang Key Laboratory of Scientific Research in Urology, No. 37 Yi-Yuan Street, Nangang District, Heilongjiang Province, Harbin, 150001, China. AD - CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun, Beijing, 100190, China. FAU - Wang, Hao AU - Wang H AD - CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun, Beijing, 100190, China. FAU - Xu, Wanhai AU - Xu W AUID- ORCID: 0000-0003-3442-7988 AD - NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, 150001, China. AD - Department of Urology, The Fourth Hospital of Harbin Medical University, Heilongjiang Key Laboratory of Scientific Research in Urology, No. 37 Yi-Yuan Street, Nangang District, Heilongjiang Province, Harbin, 150001, China. LA - eng GR - 2021YFB3801000/National Key Research and Development Program/ GR - 82172000/National Natural Science Foundation of China/ GR - U20A20385/National Natural Science Foundation of China/ GR - 81971135/National Natural Science Foundation of China/ PT - Journal Article DEP - 20220920 PL - Germany TA - Adv Mater JT - Advanced materials (Deerfield Beach, Fla.) JID - 9885358 RN - 0 (Fibronectins) RN - 80168379AG (Doxorubicin) SB - IM MH - Humans MH - Anoikis MH - Fibronectins/metabolism MH - *Carcinoma, Renal Cell/drug therapy MH - Extracellular Matrix/metabolism MH - *Kidney Neoplasms/drug therapy/metabolism MH - Doxorubicin/pharmacology/metabolism MH - Cell Line, Tumor OTO - NOTNLM OT - anoikis resistance OT - cell adhesion-mediated drug resistance OT - chemotherapy-sensitizers OT - extracellular matrices OT - self-assembly EDAT- 2022/08/26 06:00 MHDA- 2022/10/28 06:00 CRDT- 2022/08/25 06:32 PHST- 2022/08/18 00:00 [revised] PHST- 2022/04/19 00:00 [received] PHST- 2022/08/26 06:00 [pubmed] PHST- 2022/10/28 06:00 [medline] PHST- 2022/08/25 06:32 [entrez] AID - 10.1002/adma.202203518 [doi] PST - ppublish SO - Adv Mater. 2022 Oct;34(43):e2203518. doi: 10.1002/adma.202203518. Epub 2022 Sep 20.