CD41 and CD45 expression marks the angioformative initiation of neovascularisation in human haemangioblastoma

Tumour Biol. 2016 Mar;37(3):3765-74. doi: 10.1007/s13277-015-4200-x. Epub 2015 Oct 14.

Abstract

The initiation and formation of haemangioblastoma (HB) neovascularisation remain unknown, with concomitant controversy on its cytological origin. We detected HB-derived specific haematopoietic progenitors identified by surface expression of CD41 and CD45, which are similar to human embryonic vasculogenesis. CD41/CD45 cells expressed mesodermal markers, including SCL, Flk1 and c-kit. CD41 also seemed to appear before CD45 on haematopoietic progenitors. In vitro analysis showed that the CD41(+)/CD45 subpopulation gave rise to occasional primitive erythroid activity and endothelial marker expression. Meanwhile, kinetic investigation of the CD41(+)/CD45(+) subpopulation showed that some molecules, including SCL, Flk1 and c-kit, were involved in vascular formation. The CD45(+)/c-kit(+) population that lacked primitive haematopoiesis came from CD41(+) cells. Acquisition of CD45 expression by the haematopoietic progenitors was associated with advanced differentiation towards the vascular cell lineage. Taken together, the present data suggested that CD41 and CD45 expression marked the onset of HB neovascularisation and the stepwise development of the angioformative period. Our findings provide new insights into the mechanisms of HB neovascularisation and the underlying therapeutic targets of anti-vascular treatment.

Keywords: Angiogenesis; Haemangioblastomas; Molecular characterization; Neovascularisation; Vasculogenesis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cell Differentiation / genetics
  • Cell Line
  • Cell Line, Tumor
  • Cerebellar Neoplasms / blood supply
  • Cerebellar Neoplasms / genetics
  • Cerebellar Neoplasms / metabolism*
  • Female
  • Hemangioblastoma / blood supply
  • Hemangioblastoma / genetics
  • Hemangioblastoma / metabolism*
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Leukocyte Common Antigens / genetics
  • Leukocyte Common Antigens / metabolism*
  • Male
  • Microscopy, Confocal
  • Middle Aged
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism*
  • Platelet Membrane Glycoprotein IIb / genetics
  • Platelet Membrane Glycoprotein IIb / metabolism*
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Young Adult

Substances

  • Platelet Membrane Glycoprotein IIb
  • Proto-Oncogene Proteins c-kit
  • Leukocyte Common Antigens