title: Interfacing polymeric scaffolds with primary pancreatic ductal adenocarcinoma cells to develop 3D cancer models.
abstract: We analyzed the interactions between human primary cells from pancreatic ductal adenocarcinoma (PDAC) and polymeric scaffolds to develop 3D cancer models useful for mimicking the biology of this tumor. Three scaffold types based on two biocompatible polymeric formulations, such as poly(vinyl alcohol)/gelatin (PVA/G) mixture and poly(ethylene oxide terephthalate)/poly(butylene terephthalate) (PEOT/PBT) copolymer, were obtained via different techniques, namely, emulsion and freeze-drying, compression molding followed by salt leaching, and electrospinning. In this way, primary PDAC cells interfaced with different pore topographies, such as sponge-like pores of different shape and size or nanofiber interspaces. The aim of this study was to investigate the influence played by the scaffold architecture over cancerous cell growth and function. In all scaffolds, primary PDAC cells showed good viability and synthesized tumor-specific metalloproteinases (MMPs) such as MMP-2, and MMP-9. However, only sponge-like pores, obtained via emulsion-based and salt leaching-based techniques allowed for an organized cellular aggregation very similar to the native PDAC morphological structure. Differently, these cell clusters were not observed on PEOT/PBT electrospun scaffolds. MMP-2 and MMP-9, as active enzymes, resulted to be increased in PVA/G and PEOT/PBT sponges, respectively. These findings suggested that spongy scaffolds supported the generation of pancreatic tumor models with enhanced aggressiveness. In conclusion, primary PDAC cells showed diverse behaviors while interacting with different scaffold types that can be potentially exploited to create stage-specific pancreatic cancer models likely to provide new knowledge on the modulation and drug susceptibility of MMPs.
authors.affiliation: a Department of Pathology and Diagnostics ; University of Verona ; Verona , Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Ricci
authors.forename: Carlos
authors.initials: C
authors.lastname: Mota
authors.forename: Stefania
authors.initials: S
authors.lastname: Moscato
authors.forename: Delfo
authors.initials: D
authors.lastname: D'Alessandro
authors.forename: Stefano
authors.initials: S
authors.lastname: Ugel
authors.forename: Silvia
authors.initials: S
authors.lastname: Sartoris
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bronte
authors.forename: Ugo
authors.initials: U
authors.lastname: Boggi
authors.forename: Daniela
authors.initials: D
authors.lastname: Campani
authors.forename: Niccola
authors.initials: N
authors.lastname: Funel
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moroni
authors.forename: Serena
authors.initials: S
authors.lastname: Danti
mesh_terms: D001672:Biocompatible Materials / Q000494:pharmacology; D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology*; D018929:Cell Culture Techniques / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects*; D006801:Humans; D045726:Metalloproteases / Q000378:metabolism; D008954:Models, Biological; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011091:Polyesters / Q000494:pharmacology*; D011093:Polyethylene Terephthalates / Q000494:pharmacology; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D011091:Polyesters; D011093:Polyethylene Terephthalates; D045726:Metalloproteases
keywords: 2D, Bi-dimensional; 3D, Three-dimensional; BCA, Bicinchoninic acid; BSA, Bovine serum albumin; Dd, double distilled; Ds, double stranded; ECM, Extracellular matrix; G, Gelatin; HRP, Horseradish peroxidase; K-ras, Kirsten rat sarcoma viral oncogene homolog; MMP, Matrix metalloproteinase; PBS, Phosphate buffer saline; PCR, Polymer-chain reaction; PDAC, Pancreatic ductal adenocarcinoma; PEOT/PBT, Poly(ethylene oxide terephthalate)/poly(butylene terephthalate); PVA, Poly(vinyl alcohol); PanIN, Pancreatic intraepithelial neoplasia; Pancreatic adenocarcinoma; Smad4, Mothers against decapentaplegic homolog 4; TME, Tumor microenvironment.; cancer; compression molding; electrospinning; emulsion and freeze-drying; metalloproteinase 2 (MMP-2); metalloproteinase 9 (MMP-9); polyethylene oxide terephthalate (PEOT); polyvinyl alcohol (PVA); scaffold