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Multimodal therapy for synergic inhibition of tumour cell invasion and tumour-induced angiogenesis
BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN) are highly invasive tumours with frequent local and distant recurrence. Metastasis formation requires degradation of the extracellular matrix, which is fulfilled by membrane-associated proteases such as the urokinase plasminogen activa...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841144/ https://www.ncbi.nlm.nih.gov/pubmed/20222943 http://dx.doi.org/10.1186/1471-2407-10-92 |
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author | Zengel, Pamela Ramp, Diana Mack, Brigitte Zahler, Stefan Berghaus, Alexander Muehlenweg, Bernd Gires, Olivier Schmitz, Suna |
author_facet | Zengel, Pamela Ramp, Diana Mack, Brigitte Zahler, Stefan Berghaus, Alexander Muehlenweg, Bernd Gires, Olivier Schmitz, Suna |
author_sort | Zengel, Pamela |
collection | PubMed |
description | BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN) are highly invasive tumours with frequent local and distant recurrence. Metastasis formation requires degradation of the extracellular matrix, which is fulfilled by membrane-associated proteases such as the urokinase plasminogen activator (uPA). WX-UK1 is a competitive active site inhibitor of the protease function of uPA that impairs on the capacity of tumour cells to invade in vitro. METHODS: In the present study, effects of combinations of WX-UK1 with matrix metalloprotease inhibitors (MMP, galardin(®)) and cyclooxygenase-2 (COX-2, celecoxib(®)) inhibitors on tumour cell proliferation, invasion, and angiogenesis induction were evaluated. Matrigel invasion chambers and a spheroid co-cultivation model with human fibroblast served to determine the invasive potential of both FaDu (SCCHN) and HeLa (cervical carcinoma) cells, each treated with combinations of Celecoxib(®), Galardin(®), and WX-UK1. RESULTS: Blocking of single protease systems resulted in a significant 50% reduction of tumour cell invasion using WX-UK1, while the triple combination was even more effective with 80% reduction of invasion. Additionally, a sprouting assay with HUVEC was used to test the anti-angiogenetic potential of the triple combination, resulting in a 40% decrease in the sprouting rate. CONCLUSIONS: A combined approach targeting different families of proteases and cyclooxygenases represents a promising adjuvant therapy. |
format | Text |
id | pubmed-2841144 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-28411442010-03-18 Multimodal therapy for synergic inhibition of tumour cell invasion and tumour-induced angiogenesis Zengel, Pamela Ramp, Diana Mack, Brigitte Zahler, Stefan Berghaus, Alexander Muehlenweg, Bernd Gires, Olivier Schmitz, Suna BMC Cancer Research Article BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN) are highly invasive tumours with frequent local and distant recurrence. Metastasis formation requires degradation of the extracellular matrix, which is fulfilled by membrane-associated proteases such as the urokinase plasminogen activator (uPA). WX-UK1 is a competitive active site inhibitor of the protease function of uPA that impairs on the capacity of tumour cells to invade in vitro. METHODS: In the present study, effects of combinations of WX-UK1 with matrix metalloprotease inhibitors (MMP, galardin(®)) and cyclooxygenase-2 (COX-2, celecoxib(®)) inhibitors on tumour cell proliferation, invasion, and angiogenesis induction were evaluated. Matrigel invasion chambers and a spheroid co-cultivation model with human fibroblast served to determine the invasive potential of both FaDu (SCCHN) and HeLa (cervical carcinoma) cells, each treated with combinations of Celecoxib(®), Galardin(®), and WX-UK1. RESULTS: Blocking of single protease systems resulted in a significant 50% reduction of tumour cell invasion using WX-UK1, while the triple combination was even more effective with 80% reduction of invasion. Additionally, a sprouting assay with HUVEC was used to test the anti-angiogenetic potential of the triple combination, resulting in a 40% decrease in the sprouting rate. CONCLUSIONS: A combined approach targeting different families of proteases and cyclooxygenases represents a promising adjuvant therapy. BioMed Central 2010-03-11 /pmc/articles/PMC2841144/ /pubmed/20222943 http://dx.doi.org/10.1186/1471-2407-10-92 Text en Copyright ©2010 Zengel et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Zengel, Pamela Ramp, Diana Mack, Brigitte Zahler, Stefan Berghaus, Alexander Muehlenweg, Bernd Gires, Olivier Schmitz, Suna Multimodal therapy for synergic inhibition of tumour cell invasion and tumour-induced angiogenesis |
title | Multimodal therapy for synergic inhibition of tumour cell invasion and tumour-induced angiogenesis |
title_full | Multimodal therapy for synergic inhibition of tumour cell invasion and tumour-induced angiogenesis |
title_fullStr | Multimodal therapy for synergic inhibition of tumour cell invasion and tumour-induced angiogenesis |
title_full_unstemmed | Multimodal therapy for synergic inhibition of tumour cell invasion and tumour-induced angiogenesis |
title_short | Multimodal therapy for synergic inhibition of tumour cell invasion and tumour-induced angiogenesis |
title_sort | multimodal therapy for synergic inhibition of tumour cell invasion and tumour-induced angiogenesis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841144/ https://www.ncbi.nlm.nih.gov/pubmed/20222943 http://dx.doi.org/10.1186/1471-2407-10-92 |
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