Sun Ping-Hui, Chen Gang, Mason Malcolm, Jiang Wen G, Ye Lin
Cardiff China Medical Research Collaborative Institute of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
Int J Oncol. 2017 Apr;50(4):1127-1135. doi: 10.3892/ijo.2017.3884. Epub 2017 Feb 20.
A potential role may be played by receptor-type protein tyrosine phosphatase kappa (PTPRK) in angiogenesis due to its critical function in coordinating intracellular signal transduction from various receptors reliant on tyrosine phosphorylation. In the present study, we investigated the involvement of PTPRK in the cellular functions of vascular endothelial cells (HECV) and its role in angiogenesis using in vitro assays and a PTPRK knockdown vascular endothelial cell model. PTPRK knockdown in HECV cells (HECVPTPRKkd) resulted in a decrease of cell proliferation and cell-matrix adhesion; however, increased cell spreading and motility were seen. Reduced focal adhesion kinase (FAK) and paxillin protein levels were seen in the PTPRK knockdown cells which may contribute to the inhibitory effect on adhesion. HECVPTPRKkd cells were more responsive to the treatment of fibroblast growth factor (FGF) in their migration compared with the untreated control and cells treated with VEGF. Moreover, elevated c-Src and Akt1 were seen in the PTPRK knockdown cells. The FGF-promoted cell migration was remarkably suppressed by an addition of PLCγ inhibitor compared with other small inhibitors. Knockdown of PTPRK suppressed the ability of HECV cells to form tubules and also impaired the tubule formation that was induced by FGF and conditioned medium of cancer cells. Taken together, it suggests that PTPRK plays dual roles in coordinating angiogenesis. It plays a positive role in cell proliferation, adhesion and tubule formation, but suppresses cell migration, in particular, the FGF-promoted migration. PTPRK bears potential to be targeted for the prevention of tumour associated angiogenesis.
受体型蛋白酪氨酸磷酸酶κ（PTPRK）可能在血管生成中发挥潜在作用，因为它在协调依赖酪氨酸磷酸化的各种受体的细胞内信号转导中起关键作用。在本研究中，我们使用体外试验和PTPRK敲低的血管内皮细胞模型，研究了PTPRK在血管内皮细胞（HECV）细胞功能中的作用及其在血管生成中的作用。HECV细胞（HECVPTPRKkd）中的PTPRK敲低导致细胞增殖和细胞 - 基质粘附减少；然而，观察到细胞铺展和运动增加。在PTPRK敲低的细胞中观察到粘着斑激酶（FAK）和桩蛋白水平降低，这可能有助于对粘附的抑制作用。与未处理的对照和用VEGF处理的细胞相比，HECVPTPRKkd细胞在迁移中对成纤维细胞生长因子（FGF）的处理反应更强。此外，在PTPRK敲低的细胞中观察到c-Src和Akt1升高。与其他小抑制剂相比，添加PLCγ抑制剂可显著抑制FGF促进的细胞迁移。PTPRK的敲低抑制了HECV细胞形成小管的能力，也损害了由FGF和癌细胞条件培养基诱导的小管形成。综上所述，这表明PTPRK在协调血管生成中起双重作用。它在细胞增殖、粘附和小管形成中起积极作用，但抑制细胞迁移，特别是FGF促进的迁移。PTPRK具有作为预防肿瘤相关血管生成靶点的潜力。
