Autocrine and paracrine roles of VEGF/VEGFR-2 and VEGF-C/VEGFR-3 signaling in angiosarcomas of the scalp and face

Loss of autocrine endothelial-derived VEGF significantly reduces hemangiosarcoma development in conditional p53-deficient mice

“…9,10,29 Clinical studies demonstrated upregulated levels of VEGF and its receptors VEGFR1-R3, particularly in human angiosarcomas. 9 Therefore, to genetically determine the role of autocrine VEGF sources in endothelial and hematopoietic-related tumorigenesis in vivo, we generated Tie2-Cre, p53 fl/fl , VEGF fl/+ and Tie2-Cre, p53 fl/fl , VEGF fl/fl mice to conditionally delete either one or both VEGF alleles, respectively.…”

“…8 High VEGF levels have been implicated in the poor prognosis of various solid tumors, and high autocrine levels have been observed in hemangiosarcoma patients. 9,10 Excessively high levels of VEGF also result in dysfunctional vessels 11 and cytogenetically abnormal endothelial cells with centrosome overduplication and aneuploidy. 12,13 This suggests that increased VEGF levels may play important roles in the malignant transformation of endothelial cells and the initiation and/or progression of hemangiosarcomas in addition to tumor vasculature abnormalization.…”

Nephrotic syndrome unfavorable course correlates with downregulation of podocyte vascular endothelial growth factor receptor (VEGFR)-2

“…This significant pleiotropy is, however, dependent on the type of receptor present in a tissue [2]. For this reason, VEGF-C/VEGFR-2 [25,26] and VEGF-C/VEGFR-3 signaling pathway dualism [26,27] might explain a binary identity of VEGF-C manifestation.…”

Vascular-targeted agents for the treatment of angiosarcoma

“…Tokuyama et al identified increased expression of VEGF and VEGFR2 in angiosarcomas compared to capillary and cavernous haemangiomas [213]. A comparison of VEGF expression by Dim et al also suggested VEGF expression was increased in angiosarcomas compared to haemangiomas [142].…”