PMID- 28854900 OWN - NLM STAT- MEDLINE DCOM- 20180503 LR - 20181113 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 17 IP - 1 DP - 2017 Aug 30 TI - VEGFR2 regulates endothelial differentiation of colon cancer cells. PG - 593 LID - 10.1186/s12885-017-3578-9 [doi] LID - 593 AB - BACKGROUND: Recent studies suggested that cancer stem-like cells contribute to tumor vasculogenesis by differentiating into endothelial cells. However, such process is governed by still undefined mechanism. METHODS: At varying differentiation levels, three representative colon cancer cells were cultured in endothelial-inducing conditioned medium: human colon cancer cells HCT116 (HCT116) (poorly differentiated), SW480 (moderately differentiated), and HT29 (well differentiated). We tested for expression of endothelial markers (cluster of differentiation (CD) 31, CD34, and vascular endothelial (VE)-cadherin and their ability to form tube-like structures in 3D culture. We also observed VEGF secretion and expressions of endothelial markers and VEGFRs in HCT116 cells under hypoxia to simulate physiological conditions. In in vitro and in xenotransplantation experiments, VE growth factor receptor 2 (VEGFR2) antagonist SKLB1002 was used to test effect of VEGFR2 in endothelial differentiation of HCT116 cells. Expression levels of VEGFR2 and VE-cadherin were assessed by immunohistochemistry of human colon cancer tissues to evaluate clinicopathological significance of VEGFR2. RESULTS: After culturing in endothelial-inducing conditioned medium, poorly differentiated HCT116 cells expressed endothelial markers and formed tube-like structure in vitro. HCT116 cells secreted more endogenous VEGF and expressed higher VEGFR2 under hypoxia. SKLB1002 impaired endothelial differentiation in vitro and xenotransplantation experiments, suggesting a VEGFR2-dependent mechanism. Increased expression of VEGFR2 correlated with differentiation, metastasis/recurrence, and poor prognosis in 203 human colon cancer samples. Positive correlation was observed between VEGFR2 and VE-cadherin expression. CONCLUSIONS: VEGFR2 regulates endothelial differentiation of colon cancer cell and may be potential platform for anti-angiogenesis cancer therapy. FAU - Liu, Zhiyong AU - Liu Z AD - Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China. AD - The Key Laboratory of Tianjin Cancer Prevention and Treatment, Tianjin, 300060, China. AD - National Clinical Research Center for Cancer, Tianjin, 300060, China. FAU - Qi, Lisha AU - Qi L AD - Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China. AD - The Key Laboratory of Tianjin Cancer Prevention and Treatment, Tianjin, 300060, China. AD - National Clinical Research Center for Cancer, Tianjin, 300060, China. FAU - Li, Yixian AU - Li Y AD - Department of Pathology, Tianjin Medical University, Tianjin, 300070, China. FAU - Zhao, Xiulan AU - Zhao X AD - Department of Pathology, Tianjin Medical University, Tianjin, 300070, China. FAU - Sun, Baocun AU - Sun B AD - Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China. sunbaocun2014@163.com. AD - Department of Pathology, Tianjin Medical University, Tianjin, 300070, China. sunbaocun2014@163.com. AD - The Key Laboratory of Tianjin Cancer Prevention and Treatment, Tianjin, 300060, China. sunbaocun2014@163.com. AD - National Clinical Research Center for Cancer, Tianjin, 300060, China. sunbaocun2014@163.com. LA - eng PT - Journal Article DEP - 20170830 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (Antigens, CD) RN - 0 (Biomarkers, Tumor) RN - 0 (Cadherins) RN - 0 (cadherin 5) RN - EC 2.7.10.1 (KDR protein, human) RN - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2) SB - IM MH - Animals MH - Antigens, CD/metabolism MH - Biomarkers, Tumor/metabolism MH - Cadherins/metabolism MH - Cell Differentiation/*physiology MH - Cell Line, Tumor MH - Colonic Neoplasms/*metabolism/*pathology MH - Endothelial Cells/*metabolism/pathology MH - Endothelium, Vascular/*metabolism/pathology MH - Female MH - HCT116 Cells MH - HT29 Cells MH - Humans MH - Mice MH - Mice, Nude MH - Neoplasm Metastasis/pathology MH - Neoplasm Recurrence, Local/metabolism/pathology MH - Signal Transduction/physiology MH - Vascular Endothelial Growth Factor Receptor-2/*metabolism PMC - PMC5577671 OTO - NOTNLM OT - Colon cancer OT - VE-cadherin OT - VEGFR2 OT - Vasculogenesis COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: This study was approved by the Ethics Committee of Tianjin Medical University Cancer Institute and Hospital, and written informed consent was obtained from all participants. All animal experiments have been approved by Ethics Committee on animal experiments of Tianjin Medical University Cancer Institute and Hospital. CONSENT FOR PUBLICATION: Not applicable COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2017/09/01 06:00 MHDA- 2018/05/04 06:00 PMCR- 2017/08/30 CRDT- 2017/09/01 06:00 PHST- 2017/03/24 00:00 [received] PHST- 2017/08/22 00:00 [accepted] PHST- 2017/09/01 06:00 [entrez] PHST- 2017/09/01 06:00 [pubmed] PHST- 2018/05/04 06:00 [medline] PHST- 2017/08/30 00:00 [pmc-release] AID - 10.1186/s12885-017-3578-9 [pii] AID - 3578 [pii] AID - 10.1186/s12885-017-3578-9 [doi] PST - epublish SO - BMC Cancer. 2017 Aug 30;17(1):593. doi: 10.1186/s12885-017-3578-9.