Vitronectin-based hydrogels recapitulate neuroblastoma growth conditions

Monferrer Garzarán, E., Dobre, O. , Trujillo, S. , Azevedo González Oliva, M., Trubert-Paneli, A., Acevedo-León, D., Noguera, R. and Salmeron-Sanchez, M. (2022) Vitronectin-based hydrogels recapitulate neuroblastoma growth conditions. Frontiers in Cell and Developmental Biology, 10, 988699. (doi: 10.3389/fcell.2022.988699) (PMID:36425532) (PMCID:PMC9679952)

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The tumor microenvironment plays an important role in cancer development and the use of 3D in vitro systems that decouple different elements of this microenvironment is critical for the study of cancer progression. In neuroblastoma (NB), vitronectin (VN), an extracellular matrix protein, has been linked to poor prognosis and appears as a promising therapeutic target. Here, we developed hydrogels that incorporate VN into 3D polyethylene glycol (PEG) hydrogel networks to recapitulate the native NB microenvironment. The stiffness of the VN/PEG hydrogels was modulated to be comparable to the in vivo values reported for NB tissue samples. We used SK-N-BE (2) NB cells to demonstrate that PEGylated VN promotes cell adhesion as the native protein does. Furthermore, the PEGylation of VN allows its crosslinking into the hydrogel network, providing VN retention within the hydrogels that support viable cells in 3D. Confocal imaging and ELISA assays indicate that cells secrete VN also in the hydrogels and continue to reorganize their 3D environment. Overall, the 3D VN-based PEG hydrogels recapitulate the complexity of the native tumor extracellular matrix, showing that VN-cell interaction plays a key role in NB aggressiveness, and that VN could potentially be targeted in preclinical drug studies performed on the presented hydrogels.

Item Type:Articles
Additional Information:EM is supported by the Asociación Fundación Española contra el Cáncer, JAP-AECC (2018/150). This research was funded by ISCIII (FIS) and FEDER (European Regional Development Fund), grant number PI20/01107; CIBERONC (contractCB16/12/00484). OD, MG, AT-P, and MS-S acknowledge support via an EPSRC Programme Grant (EP/P001114/1).
Glasgow Author(s) Enlighten ID:Salmeron-Sanchez, Professor Manuel and Monferrer Garzarán, Ezequiel and Trubert, Alexandre and Azevedo Gonzalez Oliva, Mariana and Trujillo Munoz, Dr Sara and Dobre, Dr Oana
Authors: Monferrer Garzarán, E., Dobre, O., Trujillo, S., Azevedo González Oliva, M., Trubert-Paneli, A., Acevedo-León, D., Noguera, R., and Salmeron-Sanchez, M.
College/School:College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Frontiers in Cell and Developmental Biology
Publisher:Frontiers Media
ISSN (Online):2296-634X
Copyright Holders:Copyright © 2022 Monferrer, Dobre, Trujillo, González Oliva, Trubert-Paneli, Acevedo-León, Noguera and Salmeron-Sanchez
First Published:First published in Frontiers in Cell and Developmental Biology 10: 988699
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
173192Engineering growth factor microenvironments- a new therapeutic paradigm for regenerative medicineManuel Salmeron-SanchezEngineering and Physical Sciences Research Council (EPSRC)EP/P001114/1ENG - Biomedical Engineering