Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan.
ImPACT Research Center for Advanced Nanobiodevices, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan.
Sci Rep. 2018 Apr 30;8(1):6765. doi: 10.1038/s41598-018-24563-0.
Hepatocellular carcinoma (HCC) is a typical hyper-vascular tumor, so the understanding the mechanisms of angiogenesis in HCC is very important for its treatment. However, the influence of the exosomes secreted from HCC cells (HCC-exosomes) on angiogenesis remains poorly understood. We herein examined the effects of the exosomes secreted from HepG2 cells (HepG2-exosomes) on the lumen formation of human umbilical vein endothelial cells (HUVECs) by the imaging of angiogenesis. The degree of lumen formation of HUVECs was dependent on the number of HepG2-exosomes. The HepG2-exosomes expressed NKG2D, an activating receptor for immune cells, and HSP70, a stress-induced heat shock protein associated with angiogenesis through the vascular endothelial growth factor (VEGF) receptor. In addition, the HepG2-exosomes contained several microRNAs (miRNAs) reported to exist in the serum of HCC patients. These results suggest that the HCC-exosomes play an important role in angiogenesis. Further studies on the function of HCC-exosomes may provide a new target for HCC treatment.
肝细胞癌 (HCC) 是一种典型的富血管肿瘤,因此了解 HCC 中的血管生成机制对于其治疗非常重要。然而,HCC 细胞分泌的外泌体(HCC-exosomes)对血管生成的影响仍知之甚少。我们通过血管生成成像检查了 HepG2 细胞(HepG2-exosomes)分泌的外泌体对人脐静脉内皮细胞(HUVECs)管腔形成的影响。HUVECs 的管腔形成程度依赖于 HepG2-exosomes 的数量。HepG2-exosomes 通过血管内皮生长因子 (VEGF) 受体表达 NKG2D,一种免疫细胞的激活受体,以及 HSP70,一种与血管生成相关的应激诱导热休克蛋白。此外,HepG2-exosomes 还包含几种已报道存在于 HCC 患者血清中的 microRNAs (miRNAs)。这些结果表明 HCC-exosomes 在血管生成中发挥重要作用。进一步研究 HCC-exosomes 的功能可能为 HCC 治疗提供新的靶点。