Reuter Arik, Sckell Axel, Brandenburg Lars-Ove, Burchardt Martin, Kramer Axel, Stope Matthias B
Department of Urology, University Medicine Greifswald, Greifswald, Germany.
Department of Trauma, Hand and Reconstructive Surgery, Rostock University Medical Center, Rostock, Germany.
In Vivo. 2019 Jan-Feb;33(1):41-46. doi: 10.21873/invivo.11436.
BACKGROUND/AIM: In prostate cancer (PC), the formation of new blood vessels is stimulated by hypoxic conditions, androgens, and a number of molecular factors including microRNAs. MicroRNA-1 (miR-1) has been characterized in some tumor entities as anti-angiogenic, but this has not yet been investigated in PC.
PC cells stably overexpressing miR-1 (LNCaP-miR-1) were incubated on an in vivo hen's egg test-chorioallantoic membrane (HET-CAM) model and compared to maternal LNCaP cells. Cell growth, blood vessel organisation, and total blood vessel area were analysed.
Both matrigel-embedded LNCaP and LNCaP-miR-1 cells formed compact tumor-like cell aggregates on the CAM of the HET-CAM model. Although not quantifiable, bleeding of the CAM and remodelling of the blood vessel network in the CAM indicated an influence of miR-1 on the vascular system. The statistically significant decrease in the total surface area of blood vessels in the visible CAM section to 79.4% of control cells demonstrated the antiangiogenic properties of miR-1 for the first time.
MiR-1 had a tumor-suppressive and anti-angiogenic effect in an in vivo PC model. In the clinic, miR-1-mediated anti-angiogenesis would result in reduced tumor supply and increased hypoxic stress inside the tumor. Thus, miR-1 restoration by nucleic acid-based miR-1 mimetics would represent a promising option for future PC therapy.
背景/目的：在前列腺癌（PC）中，低氧条件、雄激素以及包括微小RNA在内的多种分子因素会刺激新血管的形成。微小RNA-1（miR-1）在一些肿瘤实体中已被证实具有抗血管生成作用，但在PC中尚未进行过此类研究。
将稳定过表达miR-1的PC细胞（LNCaP-miR-1）接种于鸡胚尿囊膜（HET-CAM）体内模型，并与亲代LNCaP细胞进行比较。分析细胞生长、血管组织及总血管面积。
基质胶包埋的LNCaP细胞和LNCaP-miR-1细胞均在HET-CAM模型的尿囊膜上形成致密的肿瘤样细胞聚集体。虽然无法进行量化，但尿囊膜出血及尿囊膜血管网络重塑表明miR-1对血管系统有影响。可见尿囊膜区域血管总表面积相较于对照细胞统计学显著下降至79.4%，首次证明了miR-1的抗血管生成特性。
在体内PC模型中，miR-1具有肿瘤抑制和抗血管生成作用。在临床上，miR-1介导的抗血管生成将导致肿瘤供血减少及肿瘤内部缺氧应激增加。因此，基于核酸的miR-1模拟物恢复miR-1水平可能是未来PC治疗的一个有前景的选择。
