Expression of vasohibin as a novel endothelium‐derived angiogenesis inhibitor in endometrial cancer

Abstract

We have previously reported on vasohibin as a novel endotheliumderived vascular endothelial growth factor (VEGF)-inducible inhibitor of angiogenesis. The aim of our present study was to define the role of vasohibin in endometrioid endometrial adenocarcinoma. We collected 78 sections of endometrial carcinoma for assessment using immunohistochemistry. Twenty-seven were well differentiated (G1), 25 were moderately differentiated (G2), and 26 were poorly differentiated endometrioid adenocarcinomas (G3). We also included 12 sections of normal cyclic endometria, six of which were in the proliferative phase and six were in the secretory phase. We investigated the expression of vasohibin, and compared it to VEGF receptor-2 (VEGFR-2: KDR/flk-1), CD34, Ki-67, VEGF-A, and D2-40 (as a lymphatic vessel marker). We assessed the ratio of vasohibin-and VEGFR-2-positive vessels in the stroma of endometrial carcinoma. Immunohistochemical assessment was classified as negative or positive based on staining intensity. Vasohibin was selectively expressed on vascular endothelial cells in both cyclic endometria and endometrial carcinomas. Vasohibin was highly expressed in the normal functional endmetrium of the secretory phase, especially in the spiral artery, and was highly expressed in all grades of endometrioid adenocarcinomas. The stromal endothelial cells in G3 expressed vasohibin and VEGFR-2 more frequently than these in G1. In endometrioid adenocarcinomas, there was a significant correlation between the expression percentage of vasohibin and that of VEGFR-2 (P < 0.0001, r 2 = 0.591). This is the first study to elucidate the correlation between expression of vasohibin in the stromal endothelial cells and that of VEGFR-2 in human carcinomas. (Cancer Sci 2008; 99: 914-919)

Vasohibin-2 Expressed in Human Serous Ovarian Adenocarcinoma Accelerates Tumor Growth by Promoting Angiogenesis

“…Previously, we investigated the expression of VASH1 under conditions accompanied by conducive to pathologic angiogenesis and showed its presence in endothelial cells of various cancers (17)(18)(19)(20)(21), atherosclerotic lesions (22), agedependent macular degeneration (23), and diabetic retinopathy (24). However, the expression of VASH2 is ill-defined.…”

Vasohibin-1 Is a Poor Prognostic Factor of Ovarian Carcinoma

“…Additionally, VASH1 expression not only in ECs of normal tissue but also ECs surrounding malignant tissue has been reported. Until the current time, VASH1 expression has been reported in carcinomas in the mammary gland (Tamaki et al 2009), large intestine (Liu et al 2015), lung (Zhang et al 2014), uterine corpus (Yoshinaga et al 2008), uterine cervix (Yoshinaga et al 2011), upper urinary tract (Miyazaki et al 2012), prostate (Kosaka et al 2013), and renal cell carcinoma (Kanomata et al 2013) in humans. These reports suggest that the expression level of VASH1 differs between cancer invasion of the same organ depending on degree and histological type.…”

EZH2 and Sonic Hedgehog Inhibition Reduce Proliferation, Migration, In Vitro Tumorigenesis, and CD133 Expression in Desmoplastic Medulloblastoma Cells

“…In cells treated with cyclopamine their levels were significantly reduced whereas in cells treated with DZNep there was no decrease in their expression (Figure 8). VASH1 is an inhibitor of tumor growth and angiogenesis that inhibits the migration, proliferation and formation of endothelial cell networks [20]. Their expression was not reduced in cells treated with DZNep compared to those treated with cyclopamine, which would explain that the treatment with DZNep showed lower migration and confluence than the cyclopamine treatment (Figure 8), probably due to the fact that DZNep did not inhibit VASH1 and TIMP3 expression, which then could act as negative regulators of migration and metastatic capacity.…”

“…For this reason, it was decided to choose concentrations of 10 and 5 μM as their IC50. Molecular and cellular experiments were performed on cyclopamine-treated DAOY cells after 48 h of exposure and DAOY cells treated with DZNep after 72 h of exposure according to results published elsewhere [20,21].…”