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, a-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.

Investigating the effect of tumor vascularization on magnetic targeting in vivo using retrospective design of experiment

“…For example, large DM results in reduced vascular surface to plasma volume ratio which therefore reduces the possibility of nanocarriers to reach and pass through the blood vessel wall [34] . Previous studies suggested that blood vessels of B16F10 tumors are 2–3-fold larger than vessels of the other three models [13] , [14] , [15] , [17] . Our histological observations are in line with the reported results where B16F10 melanoma tumors showed vessels with the large lumen, filled with erythrocytes.…”

“…and Braun et al. [14] , [15] , [16] , [17] , respectively. The vessels diameters were analyzed with either ImageJ (CT26), an in-house MATLAB algorithm (4T1), Histolab™ software (B16F10) or Fiji software (LLC).…”

“…The DM of the four tumor types used in the study are reported in the literature and are summarized in Fig. 2 d. Values ranged between 10.4 and 14.3 μm for CT26 [14] , 4T1 [15] and LLC tumors [17] . A larger vessel DM, up to 28 ± 2 μm, is reported for B16F10 tumors [16] .…”

“…CO and DM values were obtained from Refs. [11] , [12] , [20] and [14] , [15] , [16] , [17] , respectively. For MVD analysis, one-way ANOVA was performed using IBM SPSS version 20 followed by Tukey's multiple comparison test (*p < 0.05 and ***p < 0.005).…”

Jun-regulated genes promote interaction of diffuse large B-cell lymphoma with the microenvironment

“…This effect was diminished upon Jun knockdown in lymphoma cells indicating the possible role of Jun transcription factors in angiogenesis. Previous publications suggested that JunB regulates the expression of VEGF in multiple cancer cell lines [47][48][49] as well as in normal fibroblasts. 50 However, the latest study reported that selective loss of JunB in stromal cells did not affect tumor angiogenesis, 47 suggesting that activation of JunB is essential for malignant cells, but not tumor stroma, to initiate angiogenesis at the metastatic site.…”