Wnt3a Promotes the Vasculogenic Mimicry Formation of Colon Cancer via Wnt/β-Catenin Signaling.
Wnt3a Promotes the Vasculogenic Mimicry Formation of Colon Cancer via Wnt/β-Catenin Signaling.
复制标题
Wnt3a 通过 Wnt/β-连环蛋白信号传导促进结肠癌的血管生成拟态形成。
DOI：
10.3390/ijms160818564
复制
发表时间：
2015-08-10
影响因子：
5.6
通讯作者：
Sun B
中科院分区：
文献类型：
--
作者：
Qi L;Song W;Liu Z;Zhao X;Cao W;Sun B
我们以前的研究提供了证据表明，非经典Wnt信号参与调节血管生成拟态（VM）的形成。然而，经典Wnt信号传导在VM形成中的功能尚未被探索。在这项研究中，我们发现VM的存在与结肠癌组织学分化（p < 0.001）、临床分期（p < 0.001）以及转移和复发的存在（p < 0.001）有关。与VM阴性样品相比，VM阳性结肠癌样品显示增加的Wnt 3a表达（p < 0.001）和β-连环蛋白核表达（p < 0.001）。在体外，HT 29结肠癌细胞中过度调节的Wnt 3a表达促进了在三维（3-D）培养物中形成管状结构的能力，同时增加了内皮表型相关蛋白如VEGF 2和VE-钙粘蛋白的表达。小鼠异种移植模型显示，Wnt 3a过表达细胞生长成更大的肿瘤块，并形成比对照细胞更多的VM。此外，Wnt/β-catenin信号传导拮抗剂Dickkopf-1（Dkk 1）可逆转Wnt 3a过表达细胞形成管状结构的能力，并可降低VEGFR 2和VE-钙粘蛋白的表达。综上所述，我们的研究结果表明，Wnt/β-catenin信号转导参与了结肠癌VM的形成，并可能有助于开发针对VM的更准确的治疗方式。
Our previous study provided evidence that non-canonical Wnt signaling is involved in regulating vasculogenic mimicry (VM) formation. However, the functions of canonical Wnt signaling in VM formation have not yet been explored. In this study, we found the presence of VM was related to colon cancer histological differentiation (p < 0.001), the clinical stage (p < 0.001), and presence of metastasis and recurrence (p < 0.001). VM-positive colon cancer samples showed increased Wnt3a expression (p < 0.001) and β-catenin nuclear expression (p < 0.001) compared with the VM-negative samples. In vitro, over-regulated Wnt3a expression in HT29 colon cancer cells promoted the capacity to form tube-like structures in the three-dimensional (3-D) culture together with increased expression of endothelial phenotype-associated proteins such as VEGFR2 and VE-cadherin. The mouse xenograft model showed that Wnt3a-overexpressing cells grew into larger tumor masses and formed more VM than the control cells. In addition, the Wnt/β-catenin signaling antagonist Dickkopf-1(Dkk1) can reverse the capacity to form tube-like structures and can decrease the expressions of VEGFR2 and VE-cadherin in Wnt3a-overexpressing cells. Taken together, our results suggest that Wnt/β-catenin signaling is involved in VM formation in colon cancer and might contribute to the development of more accurate treatment modalities aimed at VM.