# Glioblastoma In Vitro Model That Recapitulates the Influence of the Hyaluronan Molecular Weight in Cancer Cell Motility and Permeability of the Blood-Brain Tumor Barrier

## TL;DR

A new lab model for glioblastoma shows how different sizes of hyaluronan affect cancer cell movement and brain tumor barrier permeability.

## Contribution

A novel 3D in vitro model that mimics the glioblastoma tumor microenvironment and BBB permeability influenced by hyaluronan molecular weight.

## Key findings

- Shorter hyaluronan molecules (5 kDa) increase U-87 cell invasion and cortactin overexpression.
- Higher molecular weight hyaluronan (700 kDa and 1.5 MDa) reduces cancer cell motility.
- Low molecular weight hyaluronan increases permeability of the blood-brain tumor barrier.

## Abstract

We report a glioblastoma (GBM) in vitro model
that combines an extracellular matrix (ECM)-mimicking hydrogel, hyaluronan
(HA), GBM spheroids, and a blood-brain barrier (BBB) component. The
model was designed to study the impact of the HA’s chain size
(i.e., molecular weight, Mw) on cancer cell migration and on the permeability
of the BBB. U-87 spheroids were encapsulated in alginate (Alg) hydrogels
previously loaded with HA of different Mw, i.e., 5 kDa, 700 kDa, and
1.5 MDa, mimicking the tumor microenvironment (TME) of GBM. The results
indicate that shorter HA molecules (i.e., 5 kDa) enhance the invasion
of U-87 cells, as observed by time-lapse microscopy. Moreover, this
increased cellular motility is accompanied by overexpression of cortactin
by the U-87 cells confirming an increased cancer invasive character.
In contrast, U-87 spheroids encapsulated in hydrogels that presented
HA of higher Mw, i.e., 700 kDa and 1.5 MDa, presented reduced motility,
being consistent with a limited cancer growth. Furthermore, dextran-based
permeability measurements showed that the presence of HA of low Mw
(i.e., 5 kDa) led to increased permeability of the BBB component,
a feature that is characteristic of the blood-brain tumor barrier
(BBTB). In summary, the developed 3D in vitro GBM
model effectively recapitulates key features of the TME, highlighting
the impact of the HA size on cancer cell invasion and BBB/BBTB permeability.