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Hydrogel Microwell Arrays Allow the Assessment of Protease-Associated Enhancement of Cancer Cell Aggregation and Survival
Current routine cell culture techniques are only poorly suited to capture the physiological complexity of tumor microenvironments, wherein tumor cell function is affected by intricate three-dimensional (3D), integrin-dependent cell-cell and cell-extracellular matrix (ECM) interactions. 3D cell cultu...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5003461/ https://www.ncbi.nlm.nih.gov/pubmed/27605189 http://dx.doi.org/10.3390/microarrays2030208 |
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author | Loessner, Daniela Kobel, Stefan Clements, Judith A. Lutolf, Matthias P. Hutmacher, Dietmar W. |
author_facet | Loessner, Daniela Kobel, Stefan Clements, Judith A. Lutolf, Matthias P. Hutmacher, Dietmar W. |
author_sort | Loessner, Daniela |
collection | PubMed |
description | Current routine cell culture techniques are only poorly suited to capture the physiological complexity of tumor microenvironments, wherein tumor cell function is affected by intricate three-dimensional (3D), integrin-dependent cell-cell and cell-extracellular matrix (ECM) interactions. 3D cell cultures allow the investigation of cancer-associated proteases like kallikreins as they degrade ECM proteins and alter integrin signaling, promoting malignant cell behaviors. Here, we employed a hydrogel microwell array platform to probe using a high-throughput mode how ovarian cancer cell aggregates of defined size form and survive in response to the expression of kallikreins and treatment with paclitaxel, by performing microscopic, quantitative image, gene and protein analyses dependent on the varying microwell and aggregate sizes. Paclitaxel treatment increased aggregate formation and survival of kallikrein-expressing cancer cells and levels of integrins and integrin-related factors. Cancer cell aggregate formation was improved with increasing aggregate size, thereby reducing cell death and enhancing integrin expression upon paclitaxel treatment. Therefore, hydrogel microwell arrays are a powerful tool to screen the viability of cancer cell aggregates upon modulation of protease expression, integrin engagement and anti-cancer treatment providing a micro-scaled yet high-throughput technique to assess malignant progression and drug-resistance. |
format | Online Article Text |
id | pubmed-5003461 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-50034612016-09-06 Hydrogel Microwell Arrays Allow the Assessment of Protease-Associated Enhancement of Cancer Cell Aggregation and Survival Loessner, Daniela Kobel, Stefan Clements, Judith A. Lutolf, Matthias P. Hutmacher, Dietmar W. Microarrays (Basel) Article Current routine cell culture techniques are only poorly suited to capture the physiological complexity of tumor microenvironments, wherein tumor cell function is affected by intricate three-dimensional (3D), integrin-dependent cell-cell and cell-extracellular matrix (ECM) interactions. 3D cell cultures allow the investigation of cancer-associated proteases like kallikreins as they degrade ECM proteins and alter integrin signaling, promoting malignant cell behaviors. Here, we employed a hydrogel microwell array platform to probe using a high-throughput mode how ovarian cancer cell aggregates of defined size form and survive in response to the expression of kallikreins and treatment with paclitaxel, by performing microscopic, quantitative image, gene and protein analyses dependent on the varying microwell and aggregate sizes. Paclitaxel treatment increased aggregate formation and survival of kallikrein-expressing cancer cells and levels of integrins and integrin-related factors. Cancer cell aggregate formation was improved with increasing aggregate size, thereby reducing cell death and enhancing integrin expression upon paclitaxel treatment. Therefore, hydrogel microwell arrays are a powerful tool to screen the viability of cancer cell aggregates upon modulation of protease expression, integrin engagement and anti-cancer treatment providing a micro-scaled yet high-throughput technique to assess malignant progression and drug-resistance. MDPI 2013-08-22 /pmc/articles/PMC5003461/ /pubmed/27605189 http://dx.doi.org/10.3390/microarrays2030208 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Loessner, Daniela Kobel, Stefan Clements, Judith A. Lutolf, Matthias P. Hutmacher, Dietmar W. Hydrogel Microwell Arrays Allow the Assessment of Protease-Associated Enhancement of Cancer Cell Aggregation and Survival |
title | Hydrogel Microwell Arrays Allow the Assessment of Protease-Associated Enhancement of Cancer Cell Aggregation and Survival |
title_full | Hydrogel Microwell Arrays Allow the Assessment of Protease-Associated Enhancement of Cancer Cell Aggregation and Survival |
title_fullStr | Hydrogel Microwell Arrays Allow the Assessment of Protease-Associated Enhancement of Cancer Cell Aggregation and Survival |
title_full_unstemmed | Hydrogel Microwell Arrays Allow the Assessment of Protease-Associated Enhancement of Cancer Cell Aggregation and Survival |
title_short | Hydrogel Microwell Arrays Allow the Assessment of Protease-Associated Enhancement of Cancer Cell Aggregation and Survival |
title_sort | hydrogel microwell arrays allow the assessment of protease-associated enhancement of cancer cell aggregation and survival |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5003461/ https://www.ncbi.nlm.nih.gov/pubmed/27605189 http://dx.doi.org/10.3390/microarrays2030208 |
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