Cleavage of Type I Collagen by Fibroblast Activation Protein-α Enhances Class A Scavenger Receptor Mediated Macrophage Adhesion

PLoS One. 2016 Mar 2;11(3):e0150287. doi: 10.1371/journal.pone.0150287. eCollection 2016.


Pathophysiological conditions such as fibrosis, inflammation, and tumor progression are associated with modification of the extracellular matrix (ECM). These modifications create ligands that differentially interact with cells to promote responses that drive pathological processes. Within the tumor stroma, fibroblasts are activated and increase the expression of type I collagen. In addition, activated fibroblasts specifically express fibroblast activation protein-α (FAP), a post-prolyl peptidase. Although FAP reportedly cleaves type I collagen and contributes to tumor progression, the specific pathophysiologic role of FAP is not clear. In this study, the possibility that FAP-mediated cleavage of type I collagen modulates macrophage interaction with collagen was examined using macrophage adhesion assays. Our results demonstrate that FAP selectively cleaves type I collagen resulting in increased macrophage adhesion. Increased macrophage adhesion to FAP-cleaved collagen was not affected by inhibiting integrin-mediated interactions, but was abolished in macrophages lacking the class A scavenger receptor (SR-A/CD204). Further, SR-A expressing macrophages localize with activated fibroblasts in breast tumors of MMTV-PyMT mice. Together, these results demonstrate that FAP-cleaved collagen is a substrate for SR-A-dependent macrophage adhesion, and suggest that by modifying the ECM, FAP plays a novel role in mediating communication between activated fibroblasts and macrophages.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Breast / metabolism
  • Breast / pathology
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Adhesion
  • Cells, Cultured
  • Collagen Type I / metabolism*
  • Endopeptidases
  • Female
  • Gelatinases / metabolism*
  • Humans
  • Integrins / metabolism
  • Macrophages / cytology*
  • Macrophages / metabolism
  • Macrophages / pathology
  • Membrane Proteins / metabolism*
  • Mice, Inbred C57BL
  • Recombinant Proteins / metabolism
  • Scavenger Receptors, Class A / metabolism*
  • Serine Endopeptidases / metabolism*


  • Collagen Type I
  • Integrins
  • Membrane Proteins
  • Recombinant Proteins
  • Scavenger Receptors, Class A
  • Endopeptidases
  • Serine Endopeptidases
  • fibroblast activation protein alpha
  • Gelatinases