In Cell Stress Conditions, VEGFR2 Exerts Pronounced Effects on Cell Growth in Dysplastic Barrett's Epithelial Cells
| dc.contributor.other | Zhang, Qiuyang | en |
| dc.contributor.other | Souza, Rhonda F. | en |
| dc.creator | Belli, Olivia | en |
| dc.date.accessioned | 2015-02-06T20:53:36Z | |
| dc.date.available | 2015-02-06T20:53:36Z | |
| dc.date.issued | 2015-01-26 | |
| dc.description | The 53rd Annual Medical Student Research Forum at UT Southwestern Medical Center (Monday, January 26, 2015, 2-5 p.m., D1.602) | en |
| dc.description.abstract | BACKGROUND & AIMS: Vascular endothelial growth factor (VEGF), a potent inducer of angiogenesis, recently has been shown to exert direct pro-proliferative and pro-survival effects on cancer cells through binding to its receptors, VEGFR1 and VEGFR2. In earlier studies, we showed that VEGF/VEGFR2 signaling exerts direct pro-proliferative effects on transformed Barrett's and adenocarcinoma cells in an autocrine fashion, with no significant effects on apoptosis. To explore the potential contribution of VEGFR signaling to cell growth of dysplastic Barrett's cells, we knocked down the VEGFR1 or VEGFR2 and studied the effects on cell morphology, cell number, proliferation, and apoptosis. METHODS: We used 3 high-grade dysplastic Barrett's epithelial cell lines (CP-B, CP-C, and CP-D). VEGFR1 and VEGFR2 were knocked down through stable infection with retroviral shRNA vectors. Knockdown was assessed through qRT-PCR for VEGFR1 and Western blot for VEGFR2. Cell morphology was assessed by optic microscopy. Cell numbers were assessed by cell counts at 48 hours in full growth media (FM) and under cell stress conditions (1% FM); proliferation was assessed by BrdU incorporation and apoptosis was assessed by a cell death Elisa in 1%FM. RESULTS: Knockdown of VEGFR1 was seen in 34% of CP-C, 22% of CP-D, and 0% of CP-B. Thus, we used CP-C only to assess effects of VEGFR1 knockdown. By Western blotting, we observed knockdown of VEGFR2 in CP-B and in CP-D, but not in CP-C. Thus, we used CP-B and CP-D to assess effects of VEGFR2 knockdown. We did not observed any morphology changes in the VEGFR knockdown cell lines compared to controls. In FM, dysplastic cells containing either VEGFR1 or VEGFR2 knockdown had higher cell numbers compared to control cells. In 1%FM, there was no significant difference in cell number between CP-C cells containing VEGFR1 knockdown and controls. In contrast, at 48 hours in 1%FM, CP-B and CP-D containing VEGFR2 knockdown had lower cell numbers (19.9 ± 1.3 X 104 and 10.5± 1.4 cells, respectively) compared to controls (41.4 ± 4.4 and 16.9 ± 1.6 cells). Compared to controls, VEGFR2 knockdown significantly increased BrdU incorporation in CP-B cells, even though overall cell number was decreased, whereas in CP-D, BrdU incorporation was decreased (p=0.059) along with overall cell number. Compared to controls, VEGFR2 knockdown increased apoptosis in CP-B and CP-D cells. CONCLUSIONS: VEGFR2, but not VEGFR1, contributes to cell growth of dysplastic Barrett's cells, but only under conditions of cell stress, with both pro-survival and pro-proliferative effects. These findings support a potential role for anti-VEGFR2 therapies in the treatment of high grade dysplasia in Barrett's esophagus. | en |
| dc.description.sponsorship | Southwestern Medical Foundation | en |
| dc.identifier.citation | Belli, O., Zhang, Q., & Souza, R. F. (2015, January 26). In cell stress conditions, VEGFR2 exerts pronounced effects on cell growth in dysplastic Barrett's epithelial cells. Poster presented at the 53rd Annual Medical Student Research Forum, Dallas, TX. Retrieved from https://hdl.handle.net/2152.5/1503 | en |
| dc.identifier.uri | https://hdl.handle.net/2152.5/1503 | |
| dc.language.iso | en | en |
| dc.relation.ispartofseries | 53rd Annual Medical Student Research Forum | en |
| dc.subject | Basic Research and Disease Models | en |
| dc.subject.mesh | Barrett Esophagus | en |
| dc.subject.mesh | Cell Proliferation | en |
| dc.subject.mesh | Epithelial Cells | en |
| dc.subject.mesh | Vascular Endothelial Growth Factor A | en |
| dc.subject.mesh | Vascular Endothelial Growth Factor Receptor-1 | en |
| dc.subject.mesh | Vascular Endothelial Growth Factor Receptor-2 | en |
| dc.title | In Cell Stress Conditions, VEGFR2 Exerts Pronounced Effects on Cell Growth in Dysplastic Barrett's Epithelial Cells | en |
| dc.type | Presentation | en |