Glioblastoma Tissue Slice Tandem-Cultures for Quantitative Evaluation of Inhibitory Effects on Invasion and Growth
Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, Medical Faculty, University of Leipzig, 04109 Leipzig, Germany
Rudolf-Boehm-Institute for Pharmacology and Toxicology, Medical Faculty, University of Leipzig, 04109 Leipzig, Germany
Department of Neurosurgery, Jena University Hospital, 07747 Jena, Germany
Experimental Neurosurgery, Department of Neurosurgery, Neuroscience Center, Goethe University Hospital and German Cancer Consortium (DKTK), Partner Site Frankfurt, 60438 Frankfurt am Main, Germany
Department of Neurosurgery, Section Experimental Neurosurgery and Tumor Immunology, University Hospital Carl Gustav Carus, Technical University Dresden, 01069 Dresden, Germany
German Cancer Consortium (DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
Author to whom correspondence should be addressed.
These authors contributed equally to the work.
Cancers 2020, 12(9), 2707; https://doi.org/10.3390/cancers12092707
Received: 31 July 2020 / Revised: 16 September 2020 / Accepted: 17 September 2020 / Published: 21 September 2020
Glioblastomas are very malignant and essentially incurable brain tumors. One problem is the extensive penetration of tumor cells into the adjacent normal brain tissue. Thus, the testing of novel drugs requires appropriate tumor models, preferentially avoiding animal studies. This paper describes so-called brain tissue slice tandem-culture systems. They consist of a slice of normal brain tissue and a second layer of tumor tissue. The microscopic analysis of these slice tandem-cultures allows for the simultaneous assessment of single cells invading into the normal brain tissue and the space occupying growth of the total tumor mass. It is shown that the direct application of test drugs onto the slices exerts inhibitory effects on both mechanisms. We thus describe a system mimicking the situation in glioblastoma patients. It reduces animal studies, allows for the direct application of test drugs and the precise quantitation of their inhibitory effects on tumor growth and invasion.
Glioblastomas (GBMs) are the most malignant brain tumors and are essentially incurable even after extensive surgery, radiotherapy, and chemotherapy, mainly because of extensive infiltration of tumor cells into the adjacent normal tissue. Thus, the evaluation of novel drugs in malignant glioma treatment requires sophisticated ex vivo models that approach the authentic interplay between tumor and host environment while avoiding extensive in vivo studies in animals. This paper describes the standardized setup of an organotypic brain tissue slice tandem-culture system, comprising of normal brain tissue from adult mice and tumor tissue from human glioblastoma xenografts, and explore its utility for assessing inhibitory effects of test drugs. The microscopic analysis of vertical sections of the slice tandem-cultures allows for the simultaneous assessment of (i) the invasive potential of single cells or cell aggregates and (ii) the space occupying growth of the bulk tumor mass, both contributing to malignant tumor progression. The comparison of tissue slice co-cultures with spheroids vs. tissue slice tandem-cultures using tumor xenograft slices demonstrates advantages of the xenograft tandem approach. The direct and facile application of test drugs is shown to exert inhibitory effects on bulk tumor growth and/or tumor cell invasion, and allows their precise quantitation. In conclusion, we describe a straightforward ex vivo system mimicking the in vivo situation of the tumor mass and the normal brain in GBM patients. It reduces animal studies and allows for the direct and reproducible application of test drugs and the precise quantitation of their effects on the bulk tumor mass and on the tumor’s invasive properties.