The vascular targeting agent combretastatin A-4-phosphate induces neutrophil recruitment to endothelial cells in vitro.
BACKGROUND: Combretastatin A-4-phosphate (CA-4-P) is a microtubule depolymerising agent currently in clinical trial as a tumour vascular-targeting agent. In vivo, CA-4-P causes rapid shutdown of tumour blood flow (within minutes) and a significant neutrophil infiltration at later times. MATERIALS A...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2003
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| _version_ | 1826304331175952384 |
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| author | Brooks, A Kanthou, C Cook, I Tozer, G Barber, P Vojnovic, B Nash, G Parkins, C |
| author_facet | Brooks, A Kanthou, C Cook, I Tozer, G Barber, P Vojnovic, B Nash, G Parkins, C |
| author_sort | Brooks, A |
| collection | OXFORD |
| description | BACKGROUND: Combretastatin A-4-phosphate (CA-4-P) is a microtubule depolymerising agent currently in clinical trial as a tumour vascular-targeting agent. In vivo, CA-4-P causes rapid shutdown of tumour blood flow (within minutes) and a significant neutrophil infiltration at later times. MATERIALS AND METHODS: Using an in vitro flow-cell assay, we investigated neutrophil-endothelial cell interactions and associated mechanisms, following endothelial cell exposure to CA-4-P. Cellular adhesion molecule (CAM) expression was examined using immunoblotting and immunofluorescence, and the role of CAM in neutrophil recruitment was investigated using specific blocking antibodies. RESULTS: Exposure of HUVEC to CA-4-P, resulted in significant neutrophil recruitment, and increased expression of endothelial CAM. Results of antibody studies demonstrated that endothelial CAM expression induced by CA-4-P is responsible for the observed neutrophil recruitment. DISCUSSION: This study demonstrated that the tumour vascular targeting agent, CA-4-P, directly induces endothelial CAM expression and subsequent neutrophil recruitment. In vivo, neutrophil infiltration probably contributes to CA-4-P-induced tumour cell kill. Therefore, increasing neutrophil recruitment into tumours may have potential for optimising vascular-targeted strategies for cancer therapy. |
| first_indexed | 2024-03-07T06:16:12Z |
| format | Journal article |
| id | oxford-uuid:f128434d-bd74-43d7-841c-21ea1f9dae4d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:16:12Z |
| publishDate | 2003 |
| record_format | dspace |
| spelling | oxford-uuid:f128434d-bd74-43d7-841c-21ea1f9dae4d2022-03-27T11:53:56ZThe vascular targeting agent combretastatin A-4-phosphate induces neutrophil recruitment to endothelial cells in vitro.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f128434d-bd74-43d7-841c-21ea1f9dae4dEnglishSymplectic Elements at Oxford2003Brooks, AKanthou, CCook, ITozer, GBarber, PVojnovic, BNash, GParkins, C BACKGROUND: Combretastatin A-4-phosphate (CA-4-P) is a microtubule depolymerising agent currently in clinical trial as a tumour vascular-targeting agent. In vivo, CA-4-P causes rapid shutdown of tumour blood flow (within minutes) and a significant neutrophil infiltration at later times. MATERIALS AND METHODS: Using an in vitro flow-cell assay, we investigated neutrophil-endothelial cell interactions and associated mechanisms, following endothelial cell exposure to CA-4-P. Cellular adhesion molecule (CAM) expression was examined using immunoblotting and immunofluorescence, and the role of CAM in neutrophil recruitment was investigated using specific blocking antibodies. RESULTS: Exposure of HUVEC to CA-4-P, resulted in significant neutrophil recruitment, and increased expression of endothelial CAM. Results of antibody studies demonstrated that endothelial CAM expression induced by CA-4-P is responsible for the observed neutrophil recruitment. DISCUSSION: This study demonstrated that the tumour vascular targeting agent, CA-4-P, directly induces endothelial CAM expression and subsequent neutrophil recruitment. In vivo, neutrophil infiltration probably contributes to CA-4-P-induced tumour cell kill. Therefore, increasing neutrophil recruitment into tumours may have potential for optimising vascular-targeted strategies for cancer therapy. |
| spellingShingle | Brooks, A Kanthou, C Cook, I Tozer, G Barber, P Vojnovic, B Nash, G Parkins, C The vascular targeting agent combretastatin A-4-phosphate induces neutrophil recruitment to endothelial cells in vitro. |
| title | The vascular targeting agent combretastatin A-4-phosphate induces neutrophil recruitment to endothelial cells in vitro. |
| title_full | The vascular targeting agent combretastatin A-4-phosphate induces neutrophil recruitment to endothelial cells in vitro. |
| title_fullStr | The vascular targeting agent combretastatin A-4-phosphate induces neutrophil recruitment to endothelial cells in vitro. |
| title_full_unstemmed | The vascular targeting agent combretastatin A-4-phosphate induces neutrophil recruitment to endothelial cells in vitro. |
| title_short | The vascular targeting agent combretastatin A-4-phosphate induces neutrophil recruitment to endothelial cells in vitro. |
| title_sort | vascular targeting agent combretastatin a 4 phosphate induces neutrophil recruitment to endothelial cells in vitro |
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