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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...

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Autores principales: Zengel, Pamela, Ramp, Diana, Mack, Brigitte, Zahler, Stefan, Berghaus, Alexander, Muehlenweg, Bernd, Gires, Olivier, Schmitz, Suna
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
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.
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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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