Vimentin Overexpressions Induced by Cell Hypoxia Promote Vasculogenic Mimicry by Renal Cell Carcinoma Cells.

Hao Lin,Junhong Zheng,Xincheng Liu,Bin Huang,Shaopeng Qiu,Yingkai Hong

doi:10.1155/2019/7259691

Abstract

Vasculogenic mimicry (VM), the novel approach for tumor cells to obtain blood supply, was reported to be involved in antiangiogenic resistance and poor prognosis in renal cell carcinoma (RCC). However, the molecular mechanisms underlying VM formed by RCC cells are still not clearly depicted. In the present study, we found that OS-RC-2 acquired the VM forming ability accompanied with the increased expressions of Vimentin and AXL and decreased expression of E-Cadherin by CoCl2 treatment. Downregulation of Vimentin by siRNA severely impaired the capability of OS-RC-2 and 786-O to form VM structures induced by cell hypoxia in vitro. Moreover, knockdown of Vimentin inhibited cell migration and invasion, which could be prompted by hypoxia induction in RCC cells. In our clear cell RCC tissues, we found that VM was positively correlated with Vimentin overexpression and both predicted poor prognosis. In conclusion, Vimentin plays an important role in hypoxia induced VM formation of RCC cells and targeted Vimentin might be beneficial for RCC therapy.

Highlights

Renal cell carcinoma (RCC) is among the most common cancers around the world [1]
We showed that cell hypoxia may contribute to Vasculogenic mimicry (VM) forming ability of RCC cells through epithelial-mesenchymal transition (EMT), characterized by enhancement of Vimentin and AXL and decrease of E-Cadherin expressions
We found that RCC cell lines 786-O and 769-P were able to form tubular structures on Matrigel in vitro in a cell number and cultured time dependent manner [22]

Summary

Introduction

Renal cell carcinoma (RCC) is among the most common cancers around the world [1]. It accounts for 4% of all adult malignancies in the USA in 2017 [2]. While 65% of patients with localized disease can be treated with surgery by total or partial nephrectomy, the rest of 35% who presented with metastatic RCC (mRCC) or those who relapsed after local therapy require systemic therapy [3, 4]. The management of mRCC has changed dramatically as a result of developments in target tumor vasculature therapy over the past few years, a large subset of patients treated with antiangiogenic agents will eventually experience drug resistance and disease progression [1]. The exact underlying mechanism is yet to be determined

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Conclusion