VEGFR2 regulates endothelial differentiation of colon cancer cells
Abstract 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 we...
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| Format: | Article |
| Language: | English |
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BMC
2017-08-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-017-3578-9 |
| _version_ | 1798045242198327296 |
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| author | Zhiyong Liu Lisha Qi Yixian Li Xiulan Zhao Baocun Sun |
| author_facet | Zhiyong Liu Lisha Qi Yixian Li Xiulan Zhao Baocun Sun |
| author_sort | Zhiyong Liu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-11T23:19:04Z |
| format | Article |
| id | doaj.art-86ecff28034b4d0584d006dea814d4cc |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-11T23:19:04Z |
| publishDate | 2017-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-86ecff28034b4d0584d006dea814d4cc2022-12-22T03:57:32ZengBMCBMC Cancer1471-24072017-08-0117111110.1186/s12885-017-3578-9VEGFR2 regulates endothelial differentiation of colon cancer cellsZhiyong Liu0Lisha Qi1Yixian Li2Xiulan Zhao3Baocun Sun4Department of Pathology, Tianjin Medical University Cancer Institute and HospitalDepartment of Pathology, Tianjin Medical University Cancer Institute and HospitalDepartment of Pathology, Tianjin Medical UniversityDepartment of Pathology, Tianjin Medical UniversityDepartment of Pathology, Tianjin Medical University Cancer Institute and HospitalAbstract 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.http://link.springer.com/article/10.1186/s12885-017-3578-9VEGFR2VE-cadherinVasculogenesisColon cancer |
| spellingShingle | Zhiyong Liu Lisha Qi Yixian Li Xiulan Zhao Baocun Sun VEGFR2 regulates endothelial differentiation of colon cancer cells BMC Cancer VEGFR2 VE-cadherin Vasculogenesis Colon cancer |
| title | VEGFR2 regulates endothelial differentiation of colon cancer cells |
| title_full | VEGFR2 regulates endothelial differentiation of colon cancer cells |
| title_fullStr | VEGFR2 regulates endothelial differentiation of colon cancer cells |
| title_full_unstemmed | VEGFR2 regulates endothelial differentiation of colon cancer cells |
| title_short | VEGFR2 regulates endothelial differentiation of colon cancer cells |
| title_sort | vegfr2 regulates endothelial differentiation of colon cancer cells |
| topic | VEGFR2 VE-cadherin Vasculogenesis Colon cancer |
| url | http://link.springer.com/article/10.1186/s12885-017-3578-9 |
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