Regulation of vascular endothelial growth factor in prostate cancer

Abstract

Prostate cancer (PCa) is the most common malignancy affecting men in the western world. Although radical prostatectomy and radiation therapy can successfully treat PCa in the majority of patients, up to w30% will experience local recurrence or metastatic disease. Prostate carcinogenesis and progression is typically an androgen-dependent process. For this reason, therapies for recurrent PCa target androgen biosynthesis and androgen receptor function. Such androgen deprivation therapies (ADT) are effective initially, but the duration of response is typically %24 months. Although ADT and taxane-based chemotherapy have delivered survival benefits, metastatic PCa remains incurable. Therefore, it is essential to establish the cellular and molecular mechanisms that enable localized PCas to invade and disseminate. It has long been accepted that metastases require angiogenesis. In the present review, we examine the essential role for angiogenesis in PCa metastases, and we focus in particular on the current understanding of the regulation of vascular endothelial growth factor (VEGF) in localized and metastatic PCa. We highlight recent advances in understanding the role of VEGF in regulating the interaction of cancer cells with tumor-associated immune cells during the metastatic process of PCa. We summarize the established mechanisms of transcriptional and post-transcriptional regulation of VEGF in PCa cells and outline the molecular insights obtained from preclinical animal models of PCa. Finally, we summarize the current state of anti-angiogenesis therapies for PCa and consider how existing therapies impact VEGF signaling.

Nintedanib treatment delays prostate dorsolateral lobe cancer progression in the TRAMP model: contribution to the epithelial‐stromal interaction balance

“…Pro-angiogenic pathway mechanisms stimulate tumor growth in many types of cancers, so therapies which target in tumor vasculature, as well as VEGF, PDGF, and FGF receptors, have been noticed (de Brot et al, 2015;Zhao and Adjei, 2015). Our research group has already shown the anti-PCa effects of Nintedanib in vitro, against both androgen dependent and androgen-independent human PCa cell lines (Silva et al, 2017).…”

The Androgen Receptor and VEGF: Mechanisms of Androgen-Regulated Angiogenesis in Prostate Cancer

“…VEGF regulation is complex and occurs at both transcriptional and post-transcriptional levels [21,22,23]. While the VEGF promoter lacks a TATA-binding site, it contains a GC-rich core promoter region and additional distal enhancer sites including hypoxia response elements that bind HIF1-α [24] (Figure 1A).…”

Subpathway-LNCE: Identify dysfunctional subpathways competitively regulated by lncRNAs through integrating lncRNA-mRNA expression profile and pathway topologies

“…Another significant differently expressed lncRNA was LINC00087, which competitively regulated vascular endothelial growth factor (VEGF) and cyclin D2 (CCND2). Overexpression of the differential gene VEGF could promote angiogenesis and tumourogenesis in prostate cancer, and targeting the VEGF receptor pathway had shown promising early clinical application [30, 31]. Although CCND2 was a non-differential gene, LINC00087 which competitively regulated it were differentially expressed.…”