title: Endogenous ribosomal protein L29 (RPL29): a newly identified regulator of angiogenesis in mice.
abstract: Cellular ribosomal protein L29 (RPL29) is known to be important in protein synthesis, but its function during angiogenesis has never been described before. We have shown previously that mice lacking β3-integrins support enhanced tumour angiogenesis and, therefore, deletion of endothelial αvβ3 can provide a method for discovery of novel regulators of tumour angiogenesis. Here, we describe significant upregulation of RPL29 in β3-null endothelial cells at both the mRNA and protein level. Ex vivo, we show that VEGF-stimulated microvessel sprouting was reduced significantly in Rpl29-heterozygous and Rpl29-null aortic ring assays compared with wild-type controls. Moreover, we provide in vivo evidence that RPL29 can regulate tumour angiogenesis. Tumour blood vessel density in subcutaneously grown Lewis lung carcinomas was reduced significantly in Rpl29-mutant mice. Additionally, depletion of Rpl29 using RNA interference inhibited VEGF-induced aortic ring sprouting, suggesting that anti-RPL29 strategies might have anti-angiogenic potential. Overall, our results identify that loss or depletion of RPL29 can reduce angiogenesis in vivo and ex vivo.
authors.affiliation: Centre for Tumour Biology, Barts Cancer Institute-a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, UK. dylan.jones@oncology.ox.ac.uk
authors.forename: Dylan T
authors.initials: DT
authors.lastname: Jones
authors.forename: Tanguy
authors.initials: T
authors.lastname: Lechertier
authors.forename: Louise E
authors.initials: LE
authors.lastname: Reynolds
authors.forename: Richard
authors.initials: R
authors.lastname: Mitter
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Robinson
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Kirn-Safran
authors.forename: Kairbaan M
authors.initials: KM
authors.lastname: Hodivala-Dilke
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D015870:Gene Expression; D039302:Integrin alphaVbeta3 / Q000172:deficiency / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D018919:Neovascularization, Physiologic / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D039302:Integrin alphaVbeta3; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; C084343:Rpl29 protein, mouse; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse