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

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

doi:10.1242/bio.042838

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

Biol Open. 2019 May 13;8(5):bio042838. doi: 10.1242/bio.042838.

Authors

Guoqiang Wang¹, Qiongzhi Yang², Maoyu Li¹, Ye Zhang¹, Yuxiang Cai², Xujun Liang¹, Ying Fu¹, Zhefeng Xiao¹, Minze Zhou¹, Zhongpeng Xie³, Huichao Huang¹, Yahui Huang², Yongheng Chen¹, Qiongqiong He^{4

3

2}, Fang Peng⁴, Zhuchu Chen¹

Affiliations

¹ NHC Key Laboratory of Cancer Proteomics, XiangYa Hospital, Central South University, Changsha, Hunan 410008, China.
² Department of Pathology, School of Basic Medical, Central South University, Changsha 410008, China.
³ Department of Pathology, XiangYa Hospital, Central South University, Changsha, Hunan 410008, China.
⁴ NHC Key Laboratory of Cancer Proteomics, XiangYa Hospital, Central South University, Changsha, Hunan 410008, China qiongqionghe@csu.edu.cn pengfang@csu.edu.cn.

Abstract

To 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.

Keywords: Angiogenesis; Colorectal cancer; Quantitative proteomics; Tenascin-C.