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dc.contributorUniversitat Ramon Llull. IQS
dc.contributor.authorBetriu, Nausika
dc.contributor.authorSemino, Carlos
dc.contributor.authorAndreeva, Anna
dc.date.accessioned2024-01-12T08:21:47Z
dc.date.available2024-01-12T08:21:47Z
dc.date.issued2021-09-07
dc.identifier.issn2072-6694ca
dc.identifier.urihttp://hdl.handle.net/20.500.14342/3716
dc.description.abstractThe epithelial growth factor receptor (EGFR) is a tyrosine kinase receptor that participates in many biological processes such as cell proliferation. In addition, EGFR is overexpressed in many epithelial cancers and therefore is a target for cancer therapy. Moreover, EGFR responds to lots of stimuli by internalizing into endosomes from where it can be recycled to the membrane or further sorted into lysosomes where it undergoes degradation. Two-dimensional cell cultures have been classically used to study EGFR trafficking mechanisms in cancer cells. However, it has been widely demonstrated that in 2D cultures cells are exposed to a non-physiological environment as compared to 3D cultures that provide the normal cellular conformation, matrix dimensionality and stiffness, as well as molecular gradients. Therefore, the microenvironment of solid tumors is better recreated in 3D culture models, and this is why they are becoming a more physiological alternative to study cancer physiology. Here, we develop a new model of EGFR internalization and degradation upon erlotinib treatment in pancreatic ductal adenocarcinoma (PDAC) cells cultured in a 3D self-assembling peptide scaffold. In this work, we show that treatment with the tyrosine kinase inhibitor erlotinib promotes EGFR degradation in 3D cultures of PDAC cell lines but not in 2D cultures. We also show that this receptor degradation does not occur in normal fibroblast cells, regardless of culture dimensionality. In conclusion, we demonstrate not only that erlotinib has a distinct effect on tumor and normal cells but also that pancreatic ductal adenocarcinoma cells respond differently to drug treatment when cultured in a 3D microenvironment. This study highlights the importance of culture systems that can more accurately mimic the in vivo tumor physiology.ca
dc.format.extent20 p.ca
dc.language.isoengca
dc.publisherMDPIca
dc.relation.ispartofCancersca
dc.rights© L'autor/aca
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.otherTraffickingca
dc.subject.otherDegradationca
dc.subject.otherSelf-assembling peptidesca
dc.subject.other3D cultureca
dc.subject.otherPancreatic ductal adenocarcinomaca
dc.subject.otherPDACca
dc.subject.otherDrug resistanceca
dc.subject.otherCàncer--Investigacióca
dc.titleErlotinib Promotes Ligand-Induced EGFR Degradation in 3D but Not 2D Cultures of Pancreatic Ductal Adenocarcinoma Cellsca
dc.typeinfo:eu-repo/semantics/articleca
dc.rights.accessLevelinfo:eu-repo/semantics/openAccess
dc.embargo.termscapca
dc.subject.udc616ca
dc.identifier.doihttps://www.mdpi.com/2072-6694/13/18/4504ca
dc.relation.projectIDinfo:eu-repo/grantAgreement/MICINN/PN I+D/RTI2018-096455-B-I00ca
dc.description.versioninfo:eu-repo/semantics/publishedVersionca


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