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Biomimetic Matrix for the Study of Neuroblastoma Cells: A Promising Combination of Stiffness and Retinoic Acid

30 Pages Posted: 18 May 2021 Publication Status: Under Review

See all articles by Beatrice Labat

Beatrice Labat

Université et INSA de Rouen - Laboratoire PBS UMR CNRS 6270

Nimrod Buchbinder

Rouen University Hospital - Pediatric Oncology

Sandrine Morin-Grognet

Université et INSA de Rouen

Guy Ladam

Université et INSA de Rouen

Hassan Atmani

Université et INSA de Rouen

Jean-Pierre Vannier

Université et INSA de Rouen

Abstract

Neuroblastoma is the third most common pediatric cancer composed of malignant immature cells that are usually treated pharmacologically by all trans-retinoic acid (ATRA) but sometimes, they can spontaneously differentiate into benign forms. In that context, biomimetic cell culture models are warranted tools as they can recapitulate many of the biochemical and biophysical cues of normal or pathological microenvironments. Inspired by that challenge, we developed a neuroblastoma culture system based on biomimetic LbL films of physiological biochemical composition and mechanical properties. For that, we used chondroitin sulfate A (CSA) and poly-L-lysine (PLL) that were assembled and mechanically tuned by crosslinking with genipin (GnP), a natural biocompatible crosslinker, in a relevant range of stiffness (30-160 kPa). We then assessed the adhesion, survival, motility, and differentiation of LAN-1 neuroblastoma cells. Remarkably, increasing the stiffness of the LbL films induced neuritogenesis that was strengthened by the combination with ATRA. These results highlight the crucial role of the mechanical cues of the neuroblastoma microenvironment since it can dramatically modulate the effect of pharmacologic drugs. In conclusion, our biomimetic platform offers a promising tool to help fundamental understanding and pharmacological screening of neuroblastoma differentiation and may assist the design of translational biomaterials to support neuronal regeneration.

Keywords: Tumor-like ECM, rigidity, retinoic acid, neuritogenesis, genipin

Suggested Citation

Labat, Beatrice and Buchbinder, Nimrod and Morin-Grognet, Sandrine and Ladam, Guy and Atmani, Hassan and Vannier, Jean-Pierre, Biomimetic Matrix for the Study of Neuroblastoma Cells: A Promising Combination of Stiffness and Retinoic Acid. Available at SSRN: https://ssrn.com/abstract=3849028 or http://dx.doi.org/10.2139/ssrn.3849028

Beatrice Labat (Contact Author)

Université et INSA de Rouen - Laboratoire PBS UMR CNRS 6270 ( email )

Normandy
France

Nimrod Buchbinder

Rouen University Hospital - Pediatric Oncology ( email )

37 Boulevard Gambetta
Rouen, 76000
France

Sandrine Morin-Grognet

Université et INSA de Rouen ( email )

UMR CNRS 6634
B.P. 12
Saint-Etienne du Rouvray Cedex, 76801
France

Guy Ladam

Université et INSA de Rouen ( email )

UMR CNRS 6634
B.P. 12
Saint-Etienne du Rouvray Cedex, 76801
France

Hassan Atmani

Université et INSA de Rouen ( email )

UMR CNRS 6634
B.P. 12
Saint-Etienne du Rouvray Cedex, 76801
France

Jean-Pierre Vannier

Université et INSA de Rouen ( email )

UMR CNRS 6634
B.P. 12
Saint-Etienne du Rouvray Cedex, 76801
France

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