Effect of 3D Matrix Compositions on the Efficacy ofEGFR Inhibition in Pancreatic Ductal Adenocarcinoma Cells.

Therapeutics to inhibitsignaling of epidermal growth factor receptor(EGFR) has been suggested as a potential treatment for pancreaticcancers, and two-dimensional (2D) cell culture techniques are commonlyused to identify and/or verify the therapeutic efficacy of EGFR inhibitors.However, drug targets identified from conventional cell culture techniquesmay not exhibit desired functions when these drugs are tested in animalstudies, in large part due to the complicated tumor microenvironments.Hence, it is crucial to develop a biomimetic cell culture system capableof recapitulating aspects of tumor niches for studying cancer cellfate processes under the influence of various environmental stimuli.In this study, we utilized a versatile PEG-peptide hydrogel systemto demonstrate the influence of matrix properties and EGFR inhibitionon the growth of a pancreatic ductal adenocarcinoma cell line (PANC-1).PANC-1 cells were encapsulated in 8-arm PEG-norbornene (PEG8NB) hydrogelscross-linked by matrix metalloproteinase (MMP) sensitive peptide (MMPLinker) using thiol–ene photoclick chemistry. In softhydrogels (G′ ∼ 2 kPa), cells retainedhigh initial viability and formed clusters after prolonged culture,whereas cells encapsulated in stiff hydrogels (G′∼ 12 kPa) exhibited lower initial viability and reduced proliferation.While the immobilization of an EGFR peptide inhibitor, Asn-Tyr-Gln-Gln-Asnor NYQQN, in soft hydrogels did not cause cell death, this peptideinduced significant cell apoptosis when immobilized in stiff hydrogels.Western blotting results showed that cell death was due to reducedexpression of EGFR and Akt in stiff hydrogels under the influenceof immobilized NYQQN peptide. These results shed light on the importanceand non-negligible role of matrix properties on the efficacy of antitumordrugs. [ABSTRACT FROM AUTHOR]