Endosialin/TEM-1/CD248 regulates pericyte proliferation through PDGF receptor signaling

Cancer Biol Ther. 2010 Jun 1;9(11):908-15. doi: 10.4161/cbt.9.11.11731. Epub 2010 Jun 8.


Recent reports have described several cellular phenotypes that appear to be mediated by Endosialin/TEM-1/CD248 (TEM-1), including tubule formation on matrigel, migration and proliferation. It has been shown that siRNA knock-down of TEM-1 in primary human fibroblasts resulted in reduced proliferation. However, the downstream signaling events that mediate TEM-1 function(s) currently remain unknown. In this study, we demonstrate that TEM-1 mediates proliferation of primary human pericytes through a PDGF receptor signaling pathway. Normal pericytes expressing high levels of TEM-1 were able to proliferate, respond to PDGF-BB stimulation by phosphorylating both the PDGF receptor and the MAP kinase ERK-1/2, and induce the expression of the immediate early transcription factor c-Fos. However, when TEM-1 expression was knocked-down, PDGF-BB-induced proliferation, ERK-1/2 phosphorylation, and c-Fos expression were significantly impaired. Thus, our results provide evidence for a TEM-1-dependent signal pathway that controls proliferation of human pericytes and suggest targeting this pathway for future strategies aimed at mitigating tumor angiogenesis.

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Becaplermin
  • Blotting, Western
  • Cell Line
  • Cell Proliferation*
  • Gene Expression / drug effects
  • Humans
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Models, Biological
  • Pericytes / cytology
  • Pericytes / drug effects
  • Pericytes / metabolism*
  • Phosphorylation / drug effects
  • Platelet-Derived Growth Factor / pharmacology
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Proto-Oncogene Proteins c-sis
  • RNA Interference
  • Receptors, Platelet-Derived Growth Factor / genetics
  • Receptors, Platelet-Derived Growth Factor / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction*


  • Antigens, CD
  • Antigens, Neoplasm
  • CD248 protein, human
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-sis
  • Becaplermin
  • Receptors, Platelet-Derived Growth Factor
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3