Quantitative proteomic profiling of tumor-associated vascular endothelial cells in colorectal cancer.

Guoqiang Wang,Yu-Xiang Cai,Zhefeng Xiao,Xujun Liang,Yongheng Chen,Qiongzhi Yang,Qiongqiong He,Ye Zhang,Yahui Huang,Fang Peng,Zhuchu Chen,Maoyu Li,Minze Zhou,Huichao Huang,Zhongpeng Xie,Ying Fu

doi:10.1242/bio.042838

Abstract

ABSTRACTTo investigate the global proteomic profiles of vascular endothelial cells (VECs) in the tumor microenvironment and antiangiogenic therapy for colorectal cancer (CRC), matched pairs of normal (NVECs) and tumor-associated VECs (TVECs) were purified from CRC tissues by laser capture microdissection and subjected to iTRAQ-based quantitative proteomics analysis. Here, 216 differentially expressed proteins (DEPs) were identified and used for bioinformatics analysis. Interestingly, these proteins were implicated in epithelial mesenchymal transition (EMT), ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, angiogenesis and HIF-1 signaling pathway, which may play important roles in CRC angiogenesis. Among these DEPs we found that Tenascin-C (TNC) was upregulated in TVECs of CRC and correlated with CRC multistage carcinogenesis and metastasis. Furthermore, the reduction of tumor-derived TNC could attenuate human umbilical vein endothelial cell (HUVEC) proliferation, migration and tube formation through ITGB3/FAK/Akt signaling pathway. Based on the present work, we provided a large-scale proteomic profiling of VECs in CRC with quantitative information, a certain number of potential antiangiogenic targets and a novel vision in the angiogenesis bio-mechanism of CRC.

Highlights

Tumor angiogenesis plays a vital role in creating the tumor microenvironment and is necessary for tumor growth and metastasis
Proteomic profiling of Vascular endothelial cells (VECs) in colorectal cancer (CRC) We compared the global proteomic profiles of paired Tumor-associated VECs (TVECs) and NVECs in ten patients with CRC to identify proteins and pathways that may be associated with the CRC angiogenesis
The results demonstrated that TVECs exhibited an increased dependence on processes related to focal adhesion, PI3K-Akt signaling pathway, HIF-1 signaling pathway and epithelial mesenchymal transition (EMT) (Fig. 2A,B; Fig. S1, Table S5), which might play an important role in CRC angiogenesis

Summary

Introduction

Tumor angiogenesis plays a vital role in creating the tumor microenvironment and is necessary for tumor growth and metastasis. Angiogenesis inhibitors have become important drugs in the treatment of solid tumors, including colorectal cancer (CRC) (Lopez et al, 2019; Riechelmann and Grothey, 2017). Vascular endothelial cells (VECs), which interact with tumor cells, extracellular matrix and immune killer cells, form the major components of tumor microenvironment. Tumor-associated VECs (TVECs) undergo phenotypic and epigenetic changes during tumor initiation and progression (Xiong et al, 2009). Increasing evidence indicates that proteins are primary targets of therapeutic drugs, and that proteins located in TVECs are potential therapeutic targets against tumor angiogenesis and widely used in screening antiangiogenic drugs (Kalén et al, 2009; Sonveaux, 2008)

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