MHAtriCell | Hyaluronan-rich matrices crosslinked with collagen-like peptides for 3D culture of ovarian cancer cells

Summary
In recent years creation of artificial matrices from relatively simple biomaterials that can support tumour growth in 3D is becoming an increasingly popular platform for recreating the tumour microenvironment (TME) in vitro since 3D cell culture models can more realistically reflect the in vivo TME compared with 2D monolayer cultures. In this project, we will design and fabricate novel hydrogel matrices comprising of hyaluronan crosslinked with collagen-like triple helical peptide amphiphiles (PAs). The novel HA-PA matrix will contain built-in cell adhesion sequence, HA-binding motif and matrix metalloproteinase (MMP) cleavable sequences. We will characterise these 3D hydrogel matrices to support the encapsulation and culture of ovarian cancer cells. The MMP-assisted hydrogel degradation, migration and invasion of ovarian cancer will be studied on these models using advanced electron microscopic techniques and enzyme assays. In the final phase of our study we will characterise the inhibitory potency of a highly potent and selector inhibitor of MMP-2 and MMP-9 on this system. The findings from this study will have direct implications in understanding the mechanisms associated with ovarian cancer dissemination and the newly developed hydrogel matrix can find further use as a novel biomaterial in tissue engineering and as a 3D cell culture model in cancer drug discovery and delivery.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/658351
Start date: 15-06-2015
End date: 14-06-2017
Total budget - Public funding: 183 454,80 Euro - 183 454,00 Euro
Cordis data

Original description

In recent years creation of artificial matrices from relatively simple biomaterials that can support tumour growth in 3D is becoming an increasingly popular platform for recreating the tumour microenvironment (TME) in vitro since 3D cell culture models can more realistically reflect the in vivo TME compared with 2D monolayer cultures. In this project, we will design and fabricate novel hydrogel matrices comprising of hyaluronan crosslinked with collagen-like triple helical peptide amphiphiles (PAs). The novel HA-PA matrix will contain built-in cell adhesion sequence, HA-binding motif and matrix metalloproteinase (MMP) cleavable sequences. We will characterise these 3D hydrogel matrices to support the encapsulation and culture of ovarian cancer cells. The MMP-assisted hydrogel degradation, migration and invasion of ovarian cancer will be studied on these models using advanced electron microscopic techniques and enzyme assays. In the final phase of our study we will characterise the inhibitory potency of a highly potent and selector inhibitor of MMP-2 and MMP-9 on this system. The findings from this study will have direct implications in understanding the mechanisms associated with ovarian cancer dissemination and the newly developed hydrogel matrix can find further use as a novel biomaterial in tissue engineering and as a 3D cell culture model in cancer drug discovery and delivery.

Status

CLOSED

Call topic

MSCA-IF-2014-EF

Update Date

28-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2014
MSCA-IF-2014-EF Marie Skłodowska-Curie Individual Fellowships (IF-EF)