An Omentum-inspired 3D PEG Hydrogel for Identifying ECM-drivers of Drug Resistant Ovarian Cancer

Authors

Elizabeth Brooks, University of Massachusetts AmherstFollow
Maria F. Gencoglu, University of Massachusetts Amherst
Daniel C. Corbett, University of Washington - Seattle Campus
Kelly Stevens, University of Washington
Shelly Peyton, University of Massachusetts AmherstFollow

Publication Date

2019

Journal or Book Title

APL Bioengineering

Abstract

Ovarian cancer (OvCa) is a challenging disease to treat due to poor screening techniques and late diagnosis. There is an urgent need for additional therapy options, as patients recur in 70% of cases. The limited availability of clinical treatment options could be a result of poor predictions in early stage drug screens on standard tissue culture polystyrene (TCPS). TCPS does not capture the mechanical and biochemical cues that cells experience in vivo, which can impact how cells will respond to a drug. Therefore, an in vitro model that captures some of the microenvironment features that the cells experience in vivo could provide better insights into drug responses. In this study, we formed 3D multicellular tumor spheroids (MCTS) in microwells and encapsulated them in 3D omentum-inspired hydrogels. SKOV-3 MCTS were resistant to Paclitaxel in our 3D hydrogels compared to a monolayer on TCPS. Toward clinical application, we tested cells from patients [ovarian carcinoma ascites spheroids (OCAS)] who had been treated with Paclitaxel, and drug responses predicted by using the 3D omentum-inspired hydrogels demonstrated the lack of the Paclitaxel response of these samples. Additionally, we observed the presence of collagen production around the encapsulated SKOV-3 MCTS, but not significantly on TCPS. Our results demonstrated that our 3D omentum-inspired hydrogel is an improved in vitro drug testing platform to study the OvCa drug response for patient-derived cells and helped us identify collagen 3 as a potential driver of Paclitaxel resistance in 3D.

ORCID

https://orcid.org/0000-0002-7364-8727, https://orcid.org/0000-0002-8183-7085

DOI

https://doi.org/10.1063/1.5091713

Volume

3

License

UMass Amherst Open Access Policy

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Recommended Citation

Brooks, Elizabeth; Gencoglu, Maria F.; Corbett, Daniel C.; Stevens, Kelly; and Peyton, Shelly, "An Omentum-inspired 3D PEG Hydrogel for Identifying ECM-drivers of Drug Resistant Ovarian Cancer" (2019). APL Bioengineering. 878.
https://doi.org/10.1063/1.5091713