Bioengineering contributes to new advances against childhood cancer

IBEC contributes to elucidate how the rigidity of the tumor extracellular matrix affects the aggressiveness of neuroblastoma, a cancerous tumor that affects mainly children. This opens the door to generate more accurate models to predict tumor development in patients and to work in the design of new treatments.

Neuroblastoma is the most frequent malignant tumor in the first year of life. It is caused by a genetic mutation from immature nerve cells (neuroblasts) that the fetus produces as part of its development process.

Read more…

It appears more frequently in and around the adrenal glands, but it can also occur in other areas of the abdomen and in the chest, neck and near the spine. 

Now, researchers from the Institute for Bioengineering of Catalonia (IBEC), the INCLIVA Health Research Institute and the Hospital Clínico de Valencia have made further headway in understanding how these tumors evolve by discovering how the rigidity of the tumor extracellular matrix affects the aggressiveness of neuroblastoma. 

The details of this investigation can be found in an article published this month in the journal Scientific Reports signed by a group of experts including Josep Samitier, the director of IBEC and head of the Institute’s Nanobioengineering Group. 

Previous studies indicated that the quantity and arrangement of the different elements of the tumor microenvironment could be associated with the aggressiveness of the neuroblastoma, modifying its rigidity. These works suggested that stiffer extracellular matrices generate more aggressive tumor behavior, which motivated the authors of the work published now to focus the new research addressing the stiffness of the matrix in a simple and generic way. 

To carry out the study, the researchers used a three-dimensional model obtained through 3D printing capable of generating different levels of stiffness to recreate simplified versions of tumors. Thanks to this new technology, the experts were able to see how the biomechanical properties of the tumor extracellular matrix affected the evolution of neuroblastoma. 

First of all, researchers created different hydrogel patterns with different stiffness that they modulated increasing or decreasing the amount of methacrylated alginate. After that, they cultured aggressive neuroblastic cells in these models and studied their behavior over time. 

The results of this work show that the stiffer matrices favor the adaptation and growth of the most aggressive cells over time, which proves that the rigidity of the tumor extracellular membrane plays a key role in tumor development. Furthermore, this opens the door to future therapeutic trials aimed at blocking cellular interaction with the components that confer rigidity to the tumor extracellular matrix. 

Future research will increase the complexity of the models by introducing on them stromal cells, which are non-tumor cells that make up structural tissue around the tumor cells. Moreover, the experts will add into the different models new components of the extracellular matrix to obtain characteristic patterns of the matrix associated with certain cellular behaviors. 

Researchers from the groups of Professor Rosa Noguera and Professor Josep Samitier have participated in the article as part of one of the three collaborative projects between CIBERONC and CIBER-BBN that were launched in 2018. In addition, the researcher Ezequiel Monferrer, who has a predoctoral grant from the Provincial Headquarters of Valencia of the Spanish Association Against Cancer (AECC), has also contributed to the elaboration of the study. This project has been funded by the Carlos III Health Institute (ISCIII), the European Regional Development Fund (FEDER) and the Nen Association (Nico against childhood cancer). 


Reference articleEzequiel Monferrer, Susana Martín-Vañó, Aitor Carretero, Andrea García-Lizarribar, Rebeca Burgos-Panadero, Samuel Navarro, Josep Samitier & Rosa Noguera A three-dimensional bioprinted model to evaluate the effect of stiffness on neuroblastoma cell cluster dynamics and behavior https://doi.org/10.1038/s41598-020-62986-w