An omentum-inspired 3D PEG hydrogel for identifying ECM-drivers of drug resistant ovarian cancer.
Elizabeth A BrooksMaria F GencogluDaniel C CorbettKelly R StevensShelly R PeytonPublished in: APL bioengineering (2019)
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.
Keyphrases
- induced apoptosis
- drug resistant
- drug delivery
- end stage renal disease
- cell cycle arrest
- early stage
- newly diagnosed
- tissue engineering
- wound healing
- ejection fraction
- chronic kidney disease
- hyaluronic acid
- stem cells
- multidrug resistant
- endoplasmic reticulum stress
- gene expression
- adverse drug
- signaling pathway
- oxidative stress
- emergency department
- peritoneal dialysis
- squamous cell carcinoma
- prognostic factors
- extracellular matrix
- cystic fibrosis
- drug induced
- cell proliferation
- genome wide
- radiation therapy
- climate change
- pi k akt
- lymph node
- acinetobacter baumannii
- dna methylation
- sentinel lymph node
- cell therapy
- chemotherapy induced
- cell free