M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis

J Exp Med. 2009 May 11;206(5):1089-102. doi: 10.1084/jem.20081605. Epub 2009 Apr 27.


Antiangiogenic therapy for the treatment of cancer and other neovascular diseases is desired to be selective for pathological angiogenesis and lymphangiogenesis. Macrophage colony-stimulating factor (M-CSF), a cytokine required for the differentiation of monocyte lineage cells, promotes the formation of high-density vessel networks in tumors and therefore possesses therapeutic potential as an M-CSF inhibitor. However, the physiological role of M-CSF in vascular and lymphatic development, as well as the precise mechanisms underlying the antiangiogenic effects of M-CSF inhibition, remains unclear. Moreover, therapeutic potential of M-CSF inhibition in other neovascular diseases has not yet been evaluated. We used osteopetrotic (op/op) mice to demonstrate that M-CSF deficiency reduces the abundance of LYVE-1(+) and LYVE1(-) macrophages, resulting in defects in vascular and lymphatic development. In ischemic retinopathy, M-CSF was required for pathological neovascularization but was not required for the recovery of normal vasculature. In mouse osteosarcoma, M-CSF inhibition effectively suppressed tumor angiogenesis and lymphangiogenesis, and it disorganized extracellular matrices. In contrast to VEGF blockade, interruption of M-CSF inhibition did not promote rapid vascular regrowth. Continuous M-CSF inhibition did not affect healthy vascular and lymphatic systems outside tumors. These results suggest that M-CSF-targeted therapy is an ideal strategy for treating ocular neovascular diseases and cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetic Retinopathy / drug therapy
  • Humans
  • Hyperoxia / drug therapy
  • Immunohistochemistry
  • Lymphangiogenesis / drug effects*
  • Macrophage Colony-Stimulating Factor / pharmacology*
  • Macrophage Colony-Stimulating Factor / therapeutic use*
  • Mice
  • Neoplasms / blood supply
  • Neoplasms / drug therapy
  • Neovascularization, Pathologic / prevention & control*
  • Retinal Diseases / drug therapy
  • Retinal Diseases / pathology
  • Vascular Resistance / drug effects


  • Macrophage Colony-Stimulating Factor