Fu Seng Wang, Chen Hai Ying, Lin Xiao Lu, Yang Li, Ge Zhi Zheng
Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai 200001, P.R. China.
Oncol Lett. 2017 Dec;14(6):7499-7505. doi: 10.3892/ol.2017.7111. Epub 2017 Oct 2.
Collagen triple helix repeat containing 1 (Cthrc1) is a secreted protein that has been observed to lead to poorer prognosis by inducing the invasion and metastasis in different tumors; however, it has not been demonstrated that Cthrc1 is involved in tumor angiogenesis. Immunohistochemical staining of Cthrc1 and CD31 in gastrointestinal stromal tumor tissue demonstrated that Cthrc1 is associated with microvascular density. Overexpression of Cthrc1 protein may alter the properties of human umbilical vein endothelial cells (HUVECs), including migration, invasion, tubule formation and aortic ring sprouting. Small interfering RNA-mediated knockdown of Cthrc1 was performed to verify the opposite effects. Migration and tubule formation induced by Cthrc1 overexpression in HUVECs was attenuated by inhibition of phosphorylation in extracellular-signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways. The pro-angiogenic effect of Cthcr1 is associated with increased phosphorylation of ERK and JNK in HUVECs. Silencing the expression of Cthrc1 protein may be a promising strategy to inhibit tumor angiogenesis.
含胶原蛋白三螺旋重复序列1（Cthrc1）是一种分泌蛋白，已观察到它通过诱导不同肿瘤的侵袭和转移导致较差的预后；然而，尚未证实Cthrc1参与肿瘤血管生成。胃肠道间质瘤组织中Cthrc1和CD31的免疫组织化学染色表明，Cthrc1与微血管密度相关。Cthrc1蛋白的过表达可能会改变人脐静脉内皮细胞（HUVECs）的特性，包括迁移、侵袭、小管形成和主动脉环出芽。进行小干扰RNA介导的Cthrc1敲低以验证相反的效果。细胞外信号调节蛋白激酶（ERK）和c-Jun氨基末端激酶（JNK）信号通路中磷酸化的抑制减弱了Cthrc1在HUVECs中过表达诱导的迁移和小管形成。Cthcr1的促血管生成作用与HUVECs中ERK和JNK磷酸化增加有关。沉默Cthrc1蛋白的表达可能是抑制肿瘤血管生成的一种有前景的策略。
