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Review
. 2018 Jan 4;19(1):147.
doi: 10.3390/ijms19010147.

Role of Microenvironment in Glioma Invasion: What We Learned from In Vitro Models

Ivana Manini  1 , Federica Caponnetto  2 , Anna Bartolini  3 , Tamara Ius  4 , Laura Mariuzzi  5   6 , Carla Di Loreto  7   8 , Antonio Paolo Beltrami  9 , Daniela Cesselli  10   11
Affiliations
Review

Role of Microenvironment in Glioma Invasion: What We Learned from In Vitro Models

Ivana Manini et al. Int J Mol Sci. .

Abstract

The invasion properties of glioblastoma hamper a radical surgery and are responsible for its recurrence. Understanding the invasion mechanisms is thus critical to devise new therapeutic strategies. Therefore, the creation of in vitro models that enable these mechanisms to be studied represents a crucial step. Since in vitro models represent an over-simplification of the in vivo system, in these years it has been attempted to increase the level of complexity of in vitro assays to create models that could better mimic the behaviour of the cells in vivo. These levels of complexity involved: 1. The dimension of the system, moving from two-dimensional to three-dimensional models; 2. The use of microfluidic systems; 3. The use of mixed cultures of tumour cells and cells of the tumour micro-environment in order to mimic the complex cross-talk between tumour cells and their micro-environment; 4. And the source of cells used in an attempt to move from commercial lines to patient-based models. In this review, we will summarize the evidence obtained exploring these different levels of complexity and highlighting advantages and limitations of each system used.

Keywords: 3D culture; glioblastoma; glioma-associated stem cells; invasion assay; microfluidic systems; mixed culture; personalized medicine; tumour microenvironment.

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Conflict of interest statement

The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript and in the decision to publish the results.

Figures

Figure 1
Figure 1
Preferential migration routes of glioblastoma cells. Tumour cells (dark blue) tend to invade the brain along pre-existing brain structures, such as interstitial spaces of the brain parenchyma (1); the subarachnoid space (2); the perivascular space (3) and white matter traits (4).
Figure 2
Figure 2
The glioma microenvironment. The glioma microenvironment consists, besides of tumour cells, of different cell types (including endothelial cells, astrocytes and microglia) as well as the extracellular matrix (ECM). The presence of necrotic areas can cause oxygen (O2), pH and nutrient gradients. Additionally, tumour regions are characterized by an increased stiffness with respect to the surrounding brain parenchyma. Rare stem cells (NSC, GASC and MSC) and interstitial flow, although not depicted here, paly also a role in the glioma microenvironment.
See this image and copyright information in PMC

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