Page 159 - Read Online

Topic: Brain tumor cell invasion and metastasis: anatomical,
biological and clinical considerations

Dissecting brain tumor growth and metastasis in vitro and ex vivo

Michael A. Grotzer , Anuja Neve , Martin Baumgartner 1,2
1,2
1,2
1 Department of Oncology, University Children's Hospital Zürich, Steinwiesstrasse 75, CH-8032 Zürich, Switzerland.
2 Children’s Research Center, University Children's Hospital Zürich, August-Forel Strasse 1, CH-8008 Zürich, Switzerland.
Correspondence to: Dr. Martin Baumgartner, Department of Oncology, University Children's Hospital Zürich, August-Forel Strasse 1, CH-8008
Zürich, Switzerland. E-mail: Martin.Baumgartner@kispi.uzh.ch

Dr. Martin Baumgartner is a research group leader at the Children’s Research Center of the University
Children’s Hospital Zürich and private docent at the Science Faculty of the University of Zürich.
Martin Baumgartner obtained a Ph.D. from the Pasteur Institute and the Université Pierre et Marie
Curie in Paris and did postdoctoral work at the University of California San Francisco and the
Universities of Zürich and Bern.

A B S T R AC T
Local infiltration and distal dissemination of tumor cells hamper efficacy of current treatments against central nervous system
(CNS) tumors and greatly influence mortality and therapy-induced long-term morbidity in survivors. A number of in vitro and ex
vivo assay systems have been established to better understand the infiltration and metastatic processes, to search for molecules
that specifically block tumor cell infiltration and metastatic dissemination and to pre-clinically evaluate their efficaciousness.
These systems allow analytical testing of tumor cell viability and motile and invasive capabilities in simplified and well-controlled
environments. However, the urgent need for novel anti-metastatic therapies has provided an incentive for the further development
of not only classical in vitro methods but also of novel, physiologically more relevant assay systems including organotypic brain
slice culture. In this review, using publicly available peer-reviewed primary research and review articles, we provide an overview
of a selection of in vitro and ex vivo techniques widely used to study growth and dissemination of primary metastatic brain tumors.
Furthermore, we discuss how our steadily increasing knowledge of tumor biology and the tumor microenvironment could be
integrated to improve current research methods for metastatic brain tumors. We believe that such rationally improved methods
will ultimately increase our understanding of the biology of brain tumors and facilitate the development of more efficacious anti-
metastatic treatments.

Key words: Primary brain tumor; metastasis; in vitro model system; cell migration; organotypic brain slice culture

INTRODUCTION disentangled apparently identical brain tumors as related
but functionally different tumor entities. [1-5] Within such
Impressive achievements in genomic and epigenomic single tumor entities, alterations detected in their respective
analyses of tumor tissues and individual tumor cells have metastases suggested potential driver mechanisms of tumor
revolutionized our understanding of primary brain tumors. progression. This considerably more complex image we
[6]
Alterations detected on the genome or transcriptome currently have is instrumental to better understand the highly
level in large patient cohorts in combination with our heterogeneous nature of the tumor tissue itself and of the
increasing understanding of epigenetic gene regulation have host environment interacting with it and shaping some of

This is an open access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows
Access this article online others to remix, tweak, and build upon the work non-commercially, as long as
the author is credited and the new creations are licensed under the identical
Quick Response Code: terms.
Website:
http://jcmtjournal.com For reprints contact: service@oaepublish.com

How to cite this article: Grotzer MA, Neve A, Baumgartner M.
DOI: Dissecting brain tumor growth and metastasis in vitro and ex vivo. J
10.20517/2394-4722.2016.02 Cancer Metastasis Treat 2016;2:149-62.
Received: 13-01-2016; Accepted: 09-03-2016.

©2016 Journal of Cancer Metastasis and Treatment ¦ Published by OAE Publishing Inc. 149