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Multicellular tumor spheroids: an underestimated tool is catching up again

Multicellular tumor spheroids: an underestimated tool is catching up again
Multicellular tumor spheroids: an underestimated tool is catching up again
The present article highlights the rationale, potential and flexibility of tumor spheroid mono- and cocultures for implementation into state of the art anti-cancer therapy test platforms. Unlike classical monolayer-based models, spheroids strikingly mirror the 3D cellular context and therapeutically relevant pathophysiological gradients of in vivo tumors. Some concepts for standardization and automation of spheroid culturing, monitoring and analysis are discussed, and the challenges to define the most convenient analytical endpoints for therapy testing are outlined. The potential of spheroids to contribute to either the elimination of poor drug candidates at the pre-animal and pre-clinical state or the identification of promising drugs that would fail in classical 2D cell assays is emphasised. Microtechnologies, in the form of micropatterning and microfluidics, are also discussed and offer the exciting prospect of standardized spheroid mass production to tackle high-throughput screening applications within the context of traditional laboratory settings. The extension towards more sophisticated spheroid coculture models which more closely reflect heterologous tumor tissues composed of tumor and various stromal cell types is also covered. Examples are given with particular emphasis on tumor-immune cell cocultures and their usefulness for testing novel immunotherapeutic treatment strategies. Finally, tumor cell heterogeneity and the extraordinary possibilities of putative cancer stem/tumor-initiating cell populations that can be maintained and expanded in sphere-forming assays are introduced. The relevance of the cancer stem cell hypothesis for cancer cure is highlighted, with the respective sphere cultures being envisioned as an integral tool for next generation drug development offensives.
multicellular spheroid, mass culture, micropatterning, microfluidics, spheroid coculture, immune therapy, cancer stem cells/tumor-initiating cells, cancer stem-cells, colon-carcinoma cells, in-vitro model, automatedselective dissociation, mediated photodynamic therapy, cytotoxic t-lymphocytes, breast-cancer, gene-expressionglioma-cells, hepatocellular-carcinoma
0168-1656
3-15
Hirschhaeuser, F.
473b288a-04fd-44a7-a6d0-cd45b071d680
Menne, H.
d4f73469-c0da-4b7e-9398-2e7900fa7055
Dittfeld, C.
081b3f43-c6f7-4214-8bae-6ddfb0df2db3
West, J.
f1c2e060-16c3-44c0-af70-242a1c58b968
Mueller-Klieser, W.
b79dcca6-1e96-432e-a8df-e889feb43d6f
Kunz-Schughart, L.A.
ea1e5cb7-f271-4054-ae61-e42da97e12f3
Hirschhaeuser, F.
473b288a-04fd-44a7-a6d0-cd45b071d680
Menne, H.
d4f73469-c0da-4b7e-9398-2e7900fa7055
Dittfeld, C.
081b3f43-c6f7-4214-8bae-6ddfb0df2db3
West, J.
f1c2e060-16c3-44c0-af70-242a1c58b968
Mueller-Klieser, W.
b79dcca6-1e96-432e-a8df-e889feb43d6f
Kunz-Schughart, L.A.
ea1e5cb7-f271-4054-ae61-e42da97e12f3

Hirschhaeuser, F., Menne, H., Dittfeld, C., West, J., Mueller-Klieser, W. and Kunz-Schughart, L.A. (2010) Multicellular tumor spheroids: an underestimated tool is catching up again. Journal of Biotechnology, 148 (1), 3-15. (doi:10.1016/j.jbiotec.2010.01.012).

Record type: Article

Abstract

The present article highlights the rationale, potential and flexibility of tumor spheroid mono- and cocultures for implementation into state of the art anti-cancer therapy test platforms. Unlike classical monolayer-based models, spheroids strikingly mirror the 3D cellular context and therapeutically relevant pathophysiological gradients of in vivo tumors. Some concepts for standardization and automation of spheroid culturing, monitoring and analysis are discussed, and the challenges to define the most convenient analytical endpoints for therapy testing are outlined. The potential of spheroids to contribute to either the elimination of poor drug candidates at the pre-animal and pre-clinical state or the identification of promising drugs that would fail in classical 2D cell assays is emphasised. Microtechnologies, in the form of micropatterning and microfluidics, are also discussed and offer the exciting prospect of standardized spheroid mass production to tackle high-throughput screening applications within the context of traditional laboratory settings. The extension towards more sophisticated spheroid coculture models which more closely reflect heterologous tumor tissues composed of tumor and various stromal cell types is also covered. Examples are given with particular emphasis on tumor-immune cell cocultures and their usefulness for testing novel immunotherapeutic treatment strategies. Finally, tumor cell heterogeneity and the extraordinary possibilities of putative cancer stem/tumor-initiating cell populations that can be maintained and expanded in sphere-forming assays are introduced. The relevance of the cancer stem cell hypothesis for cancer cure is highlighted, with the respective sphere cultures being envisioned as an integral tool for next generation drug development offensives.

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More information

Published date: 1 July 2010
Additional Information: ISI Document Delivery No.: 627HA Times Cited: 59 Cited Reference Count: 161 Hirschhaeuser, Franziska Menne, Heike Dittfeld, Claudia West, Jonathan Mueller-Klieser, Wolfgang Kunz-Schughart, Leoni A. International Symposium on Organotypic Tissue Culture for Substance Testing Sep, 2009 Postdam, GERMANY Elsevier science bv Amsterdam Si
Keywords: multicellular spheroid, mass culture, micropatterning, microfluidics, spheroid coculture, immune therapy, cancer stem cells/tumor-initiating cells, cancer stem-cells, colon-carcinoma cells, in-vitro model, automatedselective dissociation, mediated photodynamic therapy, cytotoxic t-lymphocytes, breast-cancer, gene-expressionglioma-cells, hepatocellular-carcinoma
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 346444
URI: http://eprints.soton.ac.uk/id/eprint/346444
ISSN: 0168-1656
PURE UUID: 9304846a-f56f-4e6a-92f0-87d2f7049509
ORCID for J. West: ORCID iD orcid.org/0000-0002-5709-6790

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Date deposited: 28 Jan 2013 11:47
Last modified: 15 Mar 2024 03:43

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Contributors

Author: F. Hirschhaeuser
Author: H. Menne
Author: C. Dittfeld
Author: J. West ORCID iD
Author: W. Mueller-Klieser
Author: L.A. Kunz-Schughart

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