M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis

Yoshiaki Kubota, Keiyo Takubo, Takatsune Shimizu, Hiroaki Ohno, Kazuo Kishi, Masabumi Shibuya, Hideyuki Saya, Toshio Suda

研究成果: Article査読

326 被引用数 (Scopus)


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.

ジャーナルJournal of Experimental Medicine
出版ステータスPublished - 2009 5月 11

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学


「M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。