Loss Of Stromal Junb Does Not Affect Tumor Growth And Angiogenesis

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, -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.What's new? JUNB is a subunit of the AP-1 transcription factor and a critical activator of Vegfa, the master regulator of angiogenesis. Here, the authors used conditional Junb knockout mice to define the role of stromal JUNB on tumor growth and angiogenesis. Surprisingly, although tumor-derived JUNB is known to critically regulate these properties, stromal, host-derived JUNB is dispensable for these processes. The study indicates that loss of stromal JUNB is well compensated by the tumor itself as well as infiltrating immune cells that provide pro-angiogenic factors and matrix metalloproteinases otherwise induced by JUNB expression in the tumor microenvironment.