The Effect of Sunitinib Treatment in Human Melanoma Xenografts: Associations with Angiogenic Profiles
The effect of antiangiogenic agents targeting the vascular endothelial growth factor A (VEGF-A) pathway has been reported to vary substantially in preclinical studies. The purpose of this study was to investigate the effect of sunitinib treatment on tumor vasculature and oxygenation in melanoma xeno...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-04-01
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| Series: | Translational Oncology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523316302212 |
| _version_ | 1818508140621070336 |
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| author | Jon-Vidar Gaustad Trude G. Simonsen Lise Mari K. Andersen Einar K. Rofstad |
| author_facet | Jon-Vidar Gaustad Trude G. Simonsen Lise Mari K. Andersen Einar K. Rofstad |
| author_sort | Jon-Vidar Gaustad |
| collection | DOAJ |
| description | The effect of antiangiogenic agents targeting the vascular endothelial growth factor A (VEGF-A) pathway has been reported to vary substantially in preclinical studies. The purpose of this study was to investigate the effect of sunitinib treatment on tumor vasculature and oxygenation in melanoma xenografts with different angiogenic profiles. A-07, U-25, D-12, or R-18 melanoma xenografts were grown in dorsal window chambers and given daily treatments of sunitinib (40 mg/kg) or vehicle. Morphologic parameters of tumor vascular networks were assessed from high-resolution transillumination images, and tumor blood supply times (BSTs) were assessed from first-pass imaging movies. Tumor hypoxia was assessed with immunohistochemistry by using pimonidazole as hypoxia marker, and the gene expression and the protein secretion rate of angiogenic factors were assessed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The melanoma lines differed substantially in the expression of VEGF-A, VEGF-C, and platelet-derived growth factor A. Sunitinib treatment reduced vessel densities and induced hypoxia in all melanoma lines, and the magnitude of the effect was associated with the gene expression and protein secretion rate of VEGF-A. Sunitinib treatment also increased vessel segment lengths, reduced the number of small-diameter vessels, and inhibited growth-induced increases in the diameter of surviving vessels but did not change BST. In conclusion, sunitinib treatment did not improve vascular function but reduced vessel density and induced hypoxia in human melanoma xenografts. The magnitude of the treatment-induced effect was associated with the VEGF-A expression of the melanoma lines. |
| first_indexed | 2024-12-10T22:27:39Z |
| format | Article |
| id | doaj.art-e666aa00b7ff4c43aa10f86e0bc9fb07 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 1944-7124 |
| language | English |
| last_indexed | 2024-12-10T22:27:39Z |
| publishDate | 2017-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-e666aa00b7ff4c43aa10f86e0bc9fb072022-12-22T01:31:08ZengElsevierTranslational Oncology1936-52331944-71242017-04-0110215816710.1016/j.tranon.2016.12.007The Effect of Sunitinib Treatment in Human Melanoma Xenografts: Associations with Angiogenic ProfilesJon-Vidar GaustadTrude G. SimonsenLise Mari K. AndersenEinar K. RofstadThe effect of antiangiogenic agents targeting the vascular endothelial growth factor A (VEGF-A) pathway has been reported to vary substantially in preclinical studies. The purpose of this study was to investigate the effect of sunitinib treatment on tumor vasculature and oxygenation in melanoma xenografts with different angiogenic profiles. A-07, U-25, D-12, or R-18 melanoma xenografts were grown in dorsal window chambers and given daily treatments of sunitinib (40 mg/kg) or vehicle. Morphologic parameters of tumor vascular networks were assessed from high-resolution transillumination images, and tumor blood supply times (BSTs) were assessed from first-pass imaging movies. Tumor hypoxia was assessed with immunohistochemistry by using pimonidazole as hypoxia marker, and the gene expression and the protein secretion rate of angiogenic factors were assessed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The melanoma lines differed substantially in the expression of VEGF-A, VEGF-C, and platelet-derived growth factor A. Sunitinib treatment reduced vessel densities and induced hypoxia in all melanoma lines, and the magnitude of the effect was associated with the gene expression and protein secretion rate of VEGF-A. Sunitinib treatment also increased vessel segment lengths, reduced the number of small-diameter vessels, and inhibited growth-induced increases in the diameter of surviving vessels but did not change BST. In conclusion, sunitinib treatment did not improve vascular function but reduced vessel density and induced hypoxia in human melanoma xenografts. The magnitude of the treatment-induced effect was associated with the VEGF-A expression of the melanoma lines.http://www.sciencedirect.com/science/article/pii/S1936523316302212 |
| spellingShingle | Jon-Vidar Gaustad Trude G. Simonsen Lise Mari K. Andersen Einar K. Rofstad The Effect of Sunitinib Treatment in Human Melanoma Xenografts: Associations with Angiogenic Profiles Translational Oncology |
| title | The Effect of Sunitinib Treatment in Human Melanoma Xenografts: Associations with Angiogenic Profiles |
| title_full | The Effect of Sunitinib Treatment in Human Melanoma Xenografts: Associations with Angiogenic Profiles |
| title_fullStr | The Effect of Sunitinib Treatment in Human Melanoma Xenografts: Associations with Angiogenic Profiles |
| title_full_unstemmed | The Effect of Sunitinib Treatment in Human Melanoma Xenografts: Associations with Angiogenic Profiles |
| title_short | The Effect of Sunitinib Treatment in Human Melanoma Xenografts: Associations with Angiogenic Profiles |
| title_sort | effect of sunitinib treatment in human melanoma xenografts associations with angiogenic profiles |
| url | http://www.sciencedirect.com/science/article/pii/S1936523316302212 |
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