| First Author | Kubota Y | Year | 2009 |
| Journal | J Exp Med | Volume | 206 |
| Issue | 5 | Pages | 1089-102 |
| PubMed ID | 19398755 | Mgi Jnum | J:148497 |
| Mgi Id | MGI:3845442 | Doi | 10.1084/jem.20081605 |
| Citation | Kubota Y, et al. (2009) M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis. J Exp Med 206(5):1089-102 |
| abstractText | 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. |
