title: In vivo imaging of lymphatic vessels in development, wound healing, inflammation, and tumor metastasis.
abstract: Lymphatic vessel growth or lymphangiogenesis occurs during embryonic development and wound healing and plays an important role in tumor metastasis and inflammatory diseases. However, the possibility of noninvasive detection and quantification of lymphangiogenesis has been lacking. Here, we present the Vegfr3(EGFPLuc) mouse model, where an EGFP-luciferase fusion protein, expressed under the endogenous transcriptional control of the Vegfr3 gene, allows the monitoring of physiological and pathological lymphangiogenesis in vivo. We show tracking of lymphatic vessel development during embryogenesis as well as lymphangiogenesis induced by specific growth factors, during wound healing and in contact hypersensitivity (CHS)--induced inflammation where we also monitor down-regulation of lymphangiogenesis by the glucocorticoid dexamethasone. Importantly, the Vegfr3-reporter allowed us to tracking tumor-induced lymphangiogenesis at the tumor periphery and in lymph nodes in association with the metastatic process. This is the first reporter mouse model for luminescence imaging of lymphangiogenesis. It should provide an important tool for studying the involvement of lymphangiogenesis in pathological processes.
authors.affiliation: Biotechnology Programme, Spanish National Cancer Research Centre, CNIO, 28029 Madrid, Spain.
authors.forename: Inés
authors.initials: I
authors.lastname: Martínez-Corral
authors.forename: David
authors.initials: D
authors.lastname: Olmeda
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Diéguez-Hurtado
authors.forename: Tuomas
authors.initials: T
authors.lastname: Tammela
authors.forename: Kari
authors.initials: K
authors.lastname: Alitalo
authors.forename: Sagrario
authors.initials: S
authors.lastname: Ortega
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology; D003952:Diagnostic Imaging / Q000379:methods*; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods; D042583:Lymphangiogenesis / Q000187:drug effects; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000196:embryology / Q000378:metabolism*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing
chemical_list: D005938:Glucocorticoids; D049452:Green Fluorescent Proteins; D003907:Dexamethasone; D008156:Luciferases; D040321:Vascular Endothelial Growth Factor Receptor-3