Expansion of Myeloid Immune Suppressor Gr+CD11b+ Cells in Tumor-Bearing Host Directly Promotes Tumor Angiogenesis

Cancer Cell. 2004 Oct;6(4):409-21. doi: 10.1016/j.ccr.2004.08.031.

Abstract

We demonstrate a novel tumor-promoting role of myeloid immune suppressor Gr+CD11b+ cells, which are evident in cancer patients and tumor-bearing animals. These cells constitute approximately 5% of total cells in tumors. Tumors coinjected with Gr+CD11b+ cells exhibited increased vascular density, vascular maturation, and decreased necrosis. These immune cells produce high levels of MMP9. Deletion of MMP9 in these cells completely abolishes their tumor-promoting ability. Gr+CD11b+ cells were also found to directly incorporate into tumor endothelium. Consistent with this observation, Gr+CD11b+ cells acquire endothelial cell (EC) properties in tumor microenvironment and proangiogenic culture conditions. Our data provide evidence that Gr+CD11b+ cells of immune origin induced by tumors directly contribute to tumor growth and vascularization by producing MMP9 and differentiating into ECs.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis
  • Bone Marrow / metabolism
  • CD11b Antigen / immunology
  • CD11b Antigen / metabolism*
  • Cell Differentiation
  • Cells, Cultured
  • Disease Progression
  • Endothelium / metabolism
  • Endothelium / pathology
  • Female
  • Humans
  • Matrix Metalloproteinase 9 / biosynthesis
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Knockout
  • Necrosis
  • Neoplasm Transplantation
  • Neoplasms / blood supply*
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neovascularization, Pathologic*
  • Stem Cell Factor / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • CD11b Antigen
  • Stem Cell Factor
  • Vascular Endothelial Growth Factor A
  • Matrix Metalloproteinase 9