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CD10 + GPR77 + Cancer-Associated Fibroblasts Promote Cancer Formation and Chemoresistance by Sustaining Cancer Stemness.
- Source :
-
Cell [Cell] 2018 Feb 08; Vol. 172 (4), pp. 841-856.e16. Date of Electronic Publication: 2018 Jan 25. - Publication Year :
- 2018
-
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 <superscript>+</superscript> GPR77 <superscript>+</superscript> CAFs promote tumor formation and chemoresistance by providing a survival niche for cancer stem cells (CSCs). Mechanistically, CD10 <superscript>+</superscript> GPR77 <superscript>+</superscript> 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 <superscript>+</superscript> GPR77 <superscript>+</superscript> 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 <superscript>+</superscript> GPR77 <superscript>+</superscript> CAF subset could be an effective therapeutic strategy against CSC-driven solid tumors.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- A549 Cells
Cell Transformation, Neoplastic pathology
Fibroblasts pathology
Humans
MCF-7 Cells
Neoplasm Proteins immunology
Neoplasms pathology
Neoplastic Stem Cells pathology
Receptor, Anaphylatoxin C5a
Cell Transformation, Neoplastic immunology
Drug Resistance, Neoplasm immunology
Fibroblasts immunology
Neoplasms immunology
Neoplastic Stem Cells immunology
Neprilysin immunology
Receptors, Chemokine immunology
Tumor Microenvironment immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 172
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 29395328
- Full Text :
- https://doi.org/10.1016/j.cell.2018.01.009