title: Loss of stromal JUNB does not affect tumor growth and angiogenesis.
abstract: The transcription factor AP-1 subunit JUNB has been shown to play a pivotal role in angiogenesis. It positively controls angiogenesis by regulating Vegfa as well as the transcriptional regulator Cbfb and its target Mmp13. In line with these findings, it has been demonstrated that tumor cell-derived JUNB promotes tumor growth and angiogenesis. In contrast to JUNB's function in tumor cells, the role of host-derived stromal JUNB has not been elucidated so far. Here, we show that ablation of Junb in stromal cells including endothelial cells (ECs), vascular smooth muscle cells (SMCs) and fibroblasts does not affect tumor growth in two different syngeneic mouse models, the B16-F1 melanoma and the Lewis lung carcinoma model. In-depth analyses of the tumors revealed that tumor angiogenesis remains unaffected as assessed by measurements of the microvascular density and relative blood volume in the tumor. Furthermore, we could show that the maturation status of the tumor vasculature, analyzed by the SMC marker expression, α-smooth muscle actin and Desmin, as well as the attachment of pericytes to the endothelium, is not changed upon ablation of Junb. Taken together, these results indicate that the pro-angiogenic functions of stromal JUNB are well compensated with regard to tumor angiogenesis and tumor growth.
authors.affiliation: Division of Signal Transduction and Growth Control DKFZ DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Braun
authors.forename: Karin
authors.initials: K
authors.lastname: Strittmatter
authors.forename: Tobias
authors.initials: T
authors.lastname: Nübel
authors.forename: Dorde
authors.initials: D
authors.lastname: Komljenovic
authors.forename: Melanie
authors.initials: M
authors.lastname: Sator-Schmitt
authors.forename: Tobias
authors.initials: T
authors.lastname: Bäuerle
authors.forename: Peter
authors.initials: P
authors.lastname: Angel
authors.forename: Marina
authors.initials: M
authors.lastname: Schorpp-Kistner
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D049109:Cell Proliferation; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D019426:Integrases / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008546:Melanoma, Experimental / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic; D020286:Pericytes / Q000378:metabolism / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C584097:JunB protein, mouse; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C045073:Cre recombinase; D019426:Integrases
keywords: AP-1; B16-F1 melanoma; JUNB; Lewis lung carcinoma; tumor angiogenesis; tumor microenvironment