MP90-09 A NEW STRATEGY FOR THE TREATMENT OF PROSTATE CANCER BY TARGETING VASOHIBIN-2

Abstract

INTRODUCTION AND OBJECTIVES: Recently, we isolated a novel angiogenic molecule, vasohibin-2 (VASH2) which is an intrinsic factor specifically expressed in activated vascular endothelial cells (ECs). Previous studies found that the expression of VASH2 was restricted to ECs and tumor cells. Although VASH2 promoting the angiogenesis in several cancers have been investigated, it has not been fully characterized yet that the VASH2 reflects the activity of tumor and the predictor of progression in prostate cancer (Pca). The aim of this study was to address the role of VASH2 expression and the treatment by targeting VASH2 in Pca. METHODS: We retrospectively analyzed the clinical records of patients with localized Pca performed radical prostatectomy and immunohistochemically analyzed the expression of VASH2. Furthermore, we analyzed the expression of VASH2 in human umbilical vein ECs (HUVEC) and Pca cell lines. The cell viability of these cells treated with anti-VASH2 antibody (V2-Ab) was determined by using the WST-1 assay. DU145 was injected subcutaneously in BALB/c nude mice and then V2-Ab was injected intraperitoneally in mice. RESULTS: The average follow-up period was 5.6 years. The expression of VASH2 was observed to ECs of microvessels in the tumor stroma and Pca cells. The density of VASH2 positive vessels were significantly associated with Gleason score and pathological T stage (p<0.05). High VASH2 density was significantly associated with preoperative PSA (p1⁄40.012), T stage (p1⁄40.026), and the intensity of VASH2 positive tumor cells (p1⁄40.048). The PSA recurrence-free survival rate was significantly worse in high VASH2 group than in low VASH2 group (p1⁄40.019). We showed that the protein level of VASH2 in HUVEC and DU145 was higher than that of the Pca cell lines (LNCap, C4-2). WST-1 assay indicated that the treatment with V2-Ab caused a decreased cell proliferation of HUVEC (67%, p<0.001) and DU145 (80%, p1⁄40.017) at high dose. We examined time course changes in DU145 tumor growth in mice. The average tumor size in the V2-Ab treatment group and in the control group on day 27 was 85mm and 389mm, respectively (p1⁄40.007). CONCLUSIONS: The present study clearly demonstrates VASH2 have the cell apoptosis mediated by V2-Ab. The results suggest that VASH2 could become a new therapeutic target in patients with CRPC.