【摘 要】
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In spite of the well-established angiogenic function in vitro, and in vivo evidence suggesting that FGF signaling is important for both normal physiological and pathological responses of the vascular
【机 构】
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Departments of Developmental Biology, Washington University School of Medicine,MO,USA
【出 处】
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3rd International Conference on Fibroblast Growth Factors (F
论文部分内容阅读
In spite of the well-established angiogenic function in vitro, and in vivo evidence suggesting that FGF signaling is important for both normal physiological and pathological responses of the vascular system, the role of FGF/FGFR signaling in vivo in endothelial cells is incompletely understood.Here, we examined a mouse model in which Fgfr1 and Fgfr2 were selectively deleted in cells of both endothelial and hematopoietic lineages, by inactivating conditional alleles for Fgfr1 and Fgfr2 (designated double flox/flox DFF) with Flk1-Cre line (resultant mouse designated Flk1-Cre:DCKO).Surprisingly, endothelial and hematopoietic FGFR1/2 is dispensable for vascular development under normal physiological conditions.Flk1-Cre:DCKO mice are viable, fertile, and healthy, and have a normal life span.However, when subjected to a two-stage skin chemical carcinogenesis protocol (DMBA/TPA), B16 melanoma and medulloblastoma cell transplantation, Flk1-Cre:DCKO mice displayed significant resistance to tumor development and impaired angiogenic response compared to their DFF control counterparts.In addition, angiogenesis in both skin wound healing and choroidal laser injury is impaired in Flk1-Cre:DCKO.These results reveal an essential requirement for FGF signaling for epithelial tumor angiogenesis and neovascularization following injury.In addition, these studies validate the endothelial cell FGFR as a potential target for enhancing wound repair and treating some cancers and diseases of the eye associated with aberrant vascular proliferation, without toxicities associated with direct manipulation of systemic FGF or VEGF activity.
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