The neutrophil protein CD177 is a novel PDPN receptor that regulates human cancer-associated fibroblast physiology

PLoS One. 2021 Dec 8;16(12):e0260800. doi: 10.1371/journal.pone.0260800. eCollection 2021.


The cancer-associated fibroblast (CAF) marker podoplanin (PDPN) is generally correlated with poor clinical outcomes in cancer patients and thus represents a promising therapeutic target. Despite its biomedical relevance, basic aspects of PDPN biology such as its cellular functions and cell surface ligands remain poorly uncharacterized, thus challenging drug development. Here, we utilize a high throughput platform to elucidate the PDPN cell surface interactome, and uncover the neutrophil protein CD177 as a new binding partner. Quantitative proteomics analysis of the CAF phosphoproteome reveals a role for PDPN in cell signaling, growth and actomyosin contractility, among other processes. Moreover, cellular assays demonstrate that CD177 is a functional antagonist, recapitulating the phenotype observed in PDPN-deficient CAFs. In sum, starting from the unbiased elucidation of the PDPN co-receptome, our work provides insights into PDPN functions and reveals the PDPN/CD177 axis as a possible modulator of fibroblast physiology in the tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cancer-Associated Fibroblasts / immunology
  • Cancer-Associated Fibroblasts / metabolism
  • Cancer-Associated Fibroblasts / pathology*
  • Cell Proliferation
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Isoantigens / genetics
  • Isoantigens / metabolism*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Prognosis
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Survival Rate
  • Tumor Cells, Cultured
  • Tumor Microenvironment*


  • Biomarkers, Tumor
  • CD177 protein, human
  • GPI-Linked Proteins
  • Isoantigens
  • Membrane Glycoproteins
  • PDPN protein, human
  • Receptors, Cell Surface

Grants and funding

The study was funded by Genentech. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.