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.
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