Header

UZH-Logo

Maintenance Infos

Investigation of brain tissue infiltration by medulloblastoma cells in an ex vivo model


Neve, Anuja; Kumar, Karthiga Santhana; Tripolitsioti, Dimitra; Grotzer, Michael A; Baumgartner, Martin (2017). Investigation of brain tissue infiltration by medulloblastoma cells in an ex vivo model. Scientific Reports, 7(1):5297.

Abstract

Medulloblastoma (MB) is a paediatric cancer of the cerebellum that can develop cerebellar and leptomeningeal metastases. Local brain tissue infiltration, the underlying cause of metastasis and relapse, remains unexplored. We developed a novel approach to investigate tissue infiltration of MB using organotypic cerebellum slice culture (OCSC). We show that cellular and structural components of cerebellar tissue in OCSCs are maintained for up to 30 days ex vivo, and that OCSCs foster tumour growth and cell proliferation. Using cell-based models of sonic hedgehog (SHH) and group 3 (G3) MB, we quantified tumour growth and infiltration and determined the morphological characteristics of the infiltrating cells. We observed basal levels of dissemination occurring in both subgroups with cells migrating either individually or collectively as clusters. Collective cerebellar tissue infiltration of SHH MB cells was further enhanced by EGF but not HGF, demonstrating differential tumour cell responses to microenvironmental cues. We found G3 cells to be hyper proliferative and observed aggressive tumour expansion even in the absence of exogenous growth factors. Our study thus provides unprecedented insights into brain tissue infiltration of SHH and G3 MB cells and reveals the cellular basis of the tumour progressing functions of EGF in SHH MB.

Abstract

Medulloblastoma (MB) is a paediatric cancer of the cerebellum that can develop cerebellar and leptomeningeal metastases. Local brain tissue infiltration, the underlying cause of metastasis and relapse, remains unexplored. We developed a novel approach to investigate tissue infiltration of MB using organotypic cerebellum slice culture (OCSC). We show that cellular and structural components of cerebellar tissue in OCSCs are maintained for up to 30 days ex vivo, and that OCSCs foster tumour growth and cell proliferation. Using cell-based models of sonic hedgehog (SHH) and group 3 (G3) MB, we quantified tumour growth and infiltration and determined the morphological characteristics of the infiltrating cells. We observed basal levels of dissemination occurring in both subgroups with cells migrating either individually or collectively as clusters. Collective cerebellar tissue infiltration of SHH MB cells was further enhanced by EGF but not HGF, demonstrating differential tumour cell responses to microenvironmental cues. We found G3 cells to be hyper proliferative and observed aggressive tumour expansion even in the absence of exogenous growth factors. Our study thus provides unprecedented insights into brain tissue infiltration of SHH and G3 MB cells and reveals the cellular basis of the tumour progressing functions of EGF in SHH MB.

Statistics

Citations

Dimensions.ai Metrics

Altmetrics

Downloads

1 download since deposited on 17 Jan 2018
1 download since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
07 Faculty of Science > Institute of Molecular Life Sciences
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:13 July 2017
Deposited On:17 Jan 2018 14:05
Last Modified:19 Feb 2018 10:27
Publisher:Nature Publishing Group
ISSN:2045-2322
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41598-017-05573-w
PubMed ID:28706234

Download

Download PDF  'Investigation of brain tissue infiltration by medulloblastoma cells in an ex vivo model'.
Preview
Content: Published Version
Filetype: PDF
Size: 3MB
View at publisher
Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)