CD10+GPR77+ Cancer-Associated Fibroblasts Promote Cancer Formation and Chemoresistance by Sustaining Cancer Stemness - PubMed (original) (raw)
. 2018 Feb 8;172(4):841-856.e16.
doi: 10.1016/j.cell.2018.01.009. Epub 2018 Jan 25.
Jianing Chen 1, Herui Yao 2, Jiang Liu 1, Shubin Yu 1, Liyan Lao 1, Minghui Wang 3, Manli Luo 4, Yue Xing 1, Fei Chen 1, Di Huang 1, Jinghua Zhao 1, Linbin Yang 1, Dan Liao 1, Fengxi Su 1, Mengfeng Li 5, Qiang Liu 1, Erwei Song 6
Affiliations
- PMID: 29395328
- DOI: 10.1016/j.cell.2018.01.009
Free article
CD10+GPR77+ Cancer-Associated Fibroblasts Promote Cancer Formation and Chemoresistance by Sustaining Cancer Stemness
Shicheng Su et al. Cell. 2018.
Free article
Abstract
Carcinoma-associated fibroblasts (CAFs) are abundant and heterogeneous stromal cells in tumor microenvironment that are critically involved in cancer progression. Here, we demonstrate that two cell-surface molecules, CD10 and GPR77, specifically define a CAF subset correlated with chemoresistance and poor survival in multiple cohorts of breast and lung cancer patients. CD10+GPR77+ CAFs promote tumor formation and chemoresistance by providing a survival niche for cancer stem cells (CSCs). Mechanistically, CD10+GPR77+ CAFs are driven by persistent NF-κB activation via p65 phosphorylation and acetylation, which is maintained by complement signaling via GPR77, a C5a receptor. Furthermore, CD10+GPR77+ CAFs promote successful engraftment of patient-derived xenografts (PDXs), and targeting these CAFs with a neutralizing anti-GPR77 antibody abolishes tumor formation and restores tumor chemosensitivity. Our study reveals a functional CAF subset that can be defined and isolated by specific cell-surface markers and suggests that targeting the CD10+GPR77+ CAF subset could be an effective therapeutic strategy against CSC-driven solid tumors.
Copyright © 2018 Elsevier Inc. All rights reserved.
Comment in
- CD10+GPR77+ Cancer-Associated Fibroblasts Promote Chemoresistance.
[No authors listed] [No authors listed] Cancer Discov. 2018 Mar;8(3):264. doi: 10.1158/2159-8290.CD-RW2018-019. Epub 2018 Feb 2. Cancer Discov. 2018. PMID: 29420180 - A Subset of Cancer-Associated Fibroblasts Determines Therapy Resistance.
Huelsken J, Hanahan D. Huelsken J, et al. Cell. 2018 Feb 8;172(4):643-644. doi: 10.1016/j.cell.2018.01.028. Cell. 2018. PMID: 29425485 - Tumour microenvironment: Fibroblast subtype provides niche for cancer stem cells.
Cully M. Cully M. Nat Rev Cancer. 2018 Feb 22;18(3):136. doi: 10.1038/nrc.2018.18. Nat Rev Cancer. 2018. PMID: 29467526 No abstract available.
Similar articles
- CCL18 signaling from tumor-associated macrophages activates fibroblasts to adopt a chemoresistance-inducing phenotype.
Zeng W, Xiong L, Wu W, Li S, Liu J, Yang L, Lao L, Huang P, Zhang M, Chen H, Miao N, Lin Z, Liu Z, Yang X, Wang J, Wang P, Song E, Yao Y, Nie Y, Chen J, Huang D. Zeng W, et al. Oncogene. 2023 Jan;42(3):224-237. doi: 10.1038/s41388-022-02540-2. Epub 2022 Nov 22. Oncogene. 2023. PMID: 36418470 Free PMC article. - FAP, CD10, and GPR77-labeled CAFs cause neoadjuvant chemotherapy resistance by inducing EMT and CSC in gastric cancer.
Zhao Z, Zhu Y. Zhao Z, et al. BMC Cancer. 2023 Jun 5;23(1):507. doi: 10.1186/s12885-023-11011-0. BMC Cancer. 2023. PMID: 37277751 Free PMC article. - CD10+GPR77+ Cancer-Associated Fibroblasts Promote Chemoresistance.
[No authors listed] [No authors listed] Cancer Discov. 2018 Mar;8(3):264. doi: 10.1158/2159-8290.CD-RW2018-019. Epub 2018 Feb 2. Cancer Discov. 2018. PMID: 29420180 - Cancer Stem Cells and Targeting Strategies.
Barbato L, Bocchetti M, Di Biase A, Regad T. Barbato L, et al. Cells. 2019 Aug 18;8(8):926. doi: 10.3390/cells8080926. Cells. 2019. PMID: 31426611 Free PMC article. Review. - The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells?
Plaks V, Kong N, Werb Z. Plaks V, et al. Cell Stem Cell. 2015 Mar 5;16(3):225-38. doi: 10.1016/j.stem.2015.02.015. Cell Stem Cell. 2015. PMID: 25748930 Free PMC article. Review.
Cited by
- Metabolic and Immunological Implications of MME+CAF-Mediated Hypoxia Signaling in Pancreatic Cancer Progression: Therapeutic Insights and Translational Opportunities.
Wang B, Pan Y, Xie Y, Wang C, Yang Y, Sun H, Yan Z, Cui Y, Li L, Zhou Y, Liu W, Pan Z. Wang B, et al. Biol Proced Online. 2024 Sep 28;26(1):29. doi: 10.1186/s12575-024-00254-1. Biol Proced Online. 2024. PMID: 39342097 Free PMC article. - CAF-Associated Genes in Breast Cancer for Novel Therapeutic Strategies.
Naito K, Sangai T, Yamashita K. Naito K, et al. Biomedicines. 2024 Aug 29;12(9):1964. doi: 10.3390/biomedicines12091964. Biomedicines. 2024. PMID: 39335478 Free PMC article. Review. - Prostate Cancer's Silent Partners: Fibroblasts and Their Influence on Glutamine Metabolism Manipulation.
Hönscheid PV, Baretton GB, Puhr M, Siciliano T, Israel JS, Stope MB, Ebersbach C, Beier AK, Thomas C, Erb HHH. Hönscheid PV, et al. Int J Mol Sci. 2024 Aug 27;25(17):9275. doi: 10.3390/ijms25179275. Int J Mol Sci. 2024. PMID: 39273225 Free PMC article. - Breast Cancer Stem Cells Upregulate IRF6 in Stromal Fibroblasts to Induce Stromagenesis.
Muralidharan H, Hansen T, Steinle A, Schumacher D, Stickeler E, Maurer J. Muralidharan H, et al. Cells. 2024 Aug 31;13(17):1466. doi: 10.3390/cells13171466. Cells. 2024. PMID: 39273037 Free PMC article. - Metabolic reprogramming and immune evasion: the interplay in the tumor microenvironment.
Zhang H, Li S, Wang D, Liu S, Xiao T, Gu W, Yang H, Wang H, Yang M, Chen P. Zhang H, et al. Biomark Res. 2024 Sep 3;12(1):96. doi: 10.1186/s40364-024-00646-1. Biomark Res. 2024. PMID: 39227970 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous