CD10+GPR77+ Cancer-Associated Fibroblasts Promote Cancer Formation and Chemoresistance by Sustaining Cancer Stemness

Cell. 2018 Feb 8;172(4):841-856.e16. doi: 10.1016/j.cell.2018.01.009. Epub 2018 Jan 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Cell Transformation, Neoplastic / immunology*
  • Cell Transformation, Neoplastic / pathology
  • Drug Resistance, Neoplasm / immunology*
  • Fibroblasts / immunology*
  • Fibroblasts / pathology
  • Humans
  • MCF-7 Cells
  • Neoplasm Proteins / immunology
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Neoplastic Stem Cells / immunology*
  • Neoplastic Stem Cells / pathology
  • Neprilysin / immunology*
  • Receptor, Anaphylatoxin C5a
  • Receptors, Chemokine / immunology*
  • Tumor Microenvironment / immunology*


  • C5aR2 protein, human
  • Neoplasm Proteins
  • Receptor, Anaphylatoxin C5a
  • Receptors, Chemokine
  • Neprilysin