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Two-Dimensional vs. Three-Dimensional In Vitro Tumor Migration and Invasion Assays

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Book cover Target Identification and Validation in Drug Discovery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 986))

Abstract

Motility and invasion are key hallmarks that distinguish benign from malignant tumors, enabling cells to cross tissue boundaries, disseminate in blood and lymph and establish metastases at distant sites. Similar properties are also utilized by activated endothelial cells during tumor-induced angiogenesis. It is now appreciated that these processes might provide a rich source of novel molecular targets with the potential for inhibitors to restrain both metastasis and neoangiogenesis. Such therapeutic strategies require assays that can rapidly and quantitatively measure cell movement and the ability to traverse physiological barriers. The need for high-throughput, however, must be balanced by assay designs that accommodate, as far as possible, the complexity of the in vivo tumor microenvironment. This chapter aims to give an overview of some commonly used migration and invasion assays to aid in the selection of a balanced portfolio of techniques for the rapid and accurate evaluation of novel therapeutic agents.

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Abbreviations

2-D:

Two-dimensional

3-D:

Three-dimensional

BBB:

Blood–brain barrier

BME:

Basement membrane extract

CAM:

Chorioallantoic membrane

CAM-DR:

Cell adhesion-mediated drug resistance

EC:

Endothelial cell

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

EHS:

Engelbreth–Holm–Swarm

EMT:

Epithelial-to-mesenchymal transition

FAK:

Focal adhesion kinase

FCS:

Fetal calf serum

GBM:

Glioblastoma

GFP:

Green fluorescent protein

HCC:

Hepatocellular carcinoma

HGF:

Hepatocyte growth factor

HIF-1:

Hypoxia-inducible factor-1

HT(S):

High-throughput (screening)

HUVEC:

Human umbilical vein endothelial cell

MMP:

Matrix metalloproteinase

MMPi:

Matrix metalloproteinase inhibitors

PD:

Pharmacodynamic

PET:

Polyethylene terephthalate

RFP:

Red fluorescent protein

s.c.:

Subcutaneously

SCC:

Squamous cell carcinoma

TIMP:

Tissue inhibitor of metalloproteinases

VEGF:

Vascular endothelial growth factor

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Acknowledgments

The authors are funded by Cancer Research UK grant number C309/A8274 (S.E.) and by the Oracle Cancer Trust (M.Z. and C.B.). We acknowledge NHS funding to the NIHR Biomedical Research Centre. We thank Maria Vinci (funded by the National Centre for the Replacement, Refinement and Reduction of Animals in Research; G1000121 ID no. 94513) and other members of the Tumour Biology and Metastasis group for critical reading of the manuscript and constructive advice.

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Authors and Affiliations

  1. Tumour Biology and Metastasis, Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, McElwain Laboratories, The Institute of Cancer Research, Surrey, UK

    Miriam Zimmermann, Carol Box & Suzanne A. Eccles

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  1. Miriam Zimmermann
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  2. Carol Box
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  3. Suzanne A. Eccles
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Editors and Affiliations

  1. Director, Department of Pharmacology, Boehringer Ingelheim RCV GmbH & Co KG, N/A, Vienna, N/A, Austria

    Jurgen Moll

  2. Project and Team Leader, Cell Biology, Nerviano Medical Sciences, Viale Pasteur 10, Nerviano, 20014, Milano, Italy

    Riccardo Colombo

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Zimmermann, M., Box, C., Eccles, S.A. (2013). Two-Dimensional vs. Three-Dimensional In Vitro Tumor Migration and Invasion Assays. In: Moll, J., Colombo, R. (eds) Target Identification and Validation in Drug Discovery. Methods in Molecular Biology, vol 986. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-311-4_15

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  • DOI: https://doi.org/10.1007/978-1-62703-311-4_15

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-310-7

  • Online ISBN: 978-1-62703-311-4

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