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Vitronectin-based hydrogels recapitulate neuroblastoma growth conditions

  • 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.

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  • PEGylated VN characterization using a TNBS assay. A. Standard curve of VN (left side) and VN free amines (in the middle) for different PEGylation ratios between VN:MAL and percentage of free amines for different PEGylation ratios shown on the right side.

  • VN distribution and retention after incorporation in the 3D hydrogel. On the top, immunofluorescence images of 3 wt% PEG hydrogels and on the bottom, 10 wt% PEG cryosections. Columns represent PEG, PEG+VN (day 0 and 3) and VN/PEG (day 0 and 3) conditions (scale bar 50 μm). Vitronectin was stained with a Cy3 secondary antibody, shown in red in the images.

  • Insets of FA images (vinculin in red) of SK-N-BE(2) cells seeded on top of unmodified or PEGylated VN for 24h (scale bar: 25 μm).

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Document Type:Article
Author:Ezequiel MonferrerORCiD, Oana DobreORCiD, Sara TrujilloORCiD, Mariana Azevedo González Oliva, Alexandre Trubert-Paneli, Delia Acevedo-León, Rosa NogueraORCiD, Manuel Salmeron-SanchezORCiD
Parent Title (English):Frontiers in Cell and Developmental Biology
First Page:1
Last Page:14
Year of first Publication:2022
Release Date:2022/10/27
Tag:extracellular matrix; neuroblastoma; polyethylene-glycol; stiffness; vitronectin
Impact:06.684 (2021)
Funding Information:Asociación Fundación Española contra el Cáncer, JAP-AECC (2018/150); ISCIII (FIS) and FEDER (European Regional Development Fund), grant number PI20/01107; CIBERONC (contractCB16/12/00484); EPSRC Programme Grant (EP/P001114/1).
Groups:Material Host Interaktionen
DDC classes:600 Technik, Medizin, angewandte Wissenschaften / 610 Medizin, Gesundheit
Open Access:Open Access
Signature:INM 2022/109
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International