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Culture media composition influences patient-derived organoid ability to predict therapeutic responses in gastrointestinal cancers.

ABSTRACT: BACKGROUNDA patient-derived organoid (PDO) platform may serve as a promising tool for translational cancer research. In this study, we evaluated PDO's ability to predict clinical response to gastrointestinal (GI) cancers.METHODSWe generated PDOs from primary and metastatic lesions of patients with GI cancers, including pancreatic ductal adenocarcinoma, colorectal adenocarcinoma, and cholangiocarcinoma. We compared PDO response with the observed clinical response for donor patients to the same treatments.RESULTSWe report an approximately 80% concordance rate between PDO and donor tumor response. Importantly, we found a profound influence of culture media on PDO phenotype, where we showed a significant difference in response to standard-of-care chemotherapies, distinct morphologies, and transcriptomes between media within the same PDO cultures.CONCLUSIONWhile we demonstrate a high concordance rate between donor tumor and PDO, these studies also showed the important role of culture media when using PDOs to inform treatment selection and predict response across a spectrum of GI cancers.TRIAL REGISTRATIONNot applicable.FUNDINGThe Joan F. & Richard A. Abdoo Family Fund in Colorectal Cancer Research, GI Cancer program of the Mayo Clinic Cancer Center, Mayo Clinic SPORE in Pancreatic Cancer, Center of Individualized Medicine (Mayo Clinic), Department of Laboratory Medicine and Pathology (Mayo Clinic), Incyte Pharmaceuticals and Mayo Clinic Hepatobiliary SPORE, University of Minnesota-Mayo Clinic Partnership, and the Early Therapeutic program (Department of Oncology, Mayo Clinic).

SUBMITTER: Hogenson TL

PROVIDER: S-EPMC9746806 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Culture media composition influences patient-derived organoid ability to predict therapeutic responses in gastrointestinal cancers.

Hogenson Tara L TL Xie Hao H Phillips William J WJ Toruner Merih D MD Li Jenny J JJ Horn Isaac P IP Kennedy Devin J DJ Almada Luciana L LL Marks David L DL Carr Ryan M RM Toruner Murat M Sigafoos Ashley N AN Koenig-Kappes Amanda N AN Olson Rachel Lo RL Tolosa Ezequiel J EJ Zhang Cheng C Li Hu H Doles Jason D JD Bleeker Jonathan J Barrett Michael T MT Boyum James H JH Kipp Benjamin R BR Mahipal Amit A Hubbard Joleen M JM Scheffler Hanson Temperance J TJ Petersen Gloria M GM Dasari Surendra S Oberg Ann L AL Truty Mark J MJ Graham Rondell P RP Levy Michael J MJ Zhu Mojun M Billadeau Daniel D DD Adjei Alex A AA Dusetti Nelson N Iovanna Juan L JL Bekaii-Saab Tanios S TS Ma Wen Wee WW Fernandez-Zapico Martin E ME

JCI insight 20221122 22

BACKGROUNDA patient-derived organoid (PDO) platform may serve as a promising tool for translational cancer research. In this study, we evaluated PDO's ability to predict clinical response to gastrointestinal (GI) cancers.METHODSWe generated PDOs from primary and metastatic lesions of patients with GI cancers, including pancreatic ductal adenocarcinoma, colorectal adenocarcinoma, and cholangiocarcinoma. We compared PDO response with the observed clinical response for donor patients to the same tr ...[more]

PMID: 36256477

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Project description:The potential applications of nanomaterials as drug delivery systems and in other products continue to expand. Upon introduction into physiological environments and driven by energetics, nanomaterials readily associate proteins forming a protein corona (PC) on their surface. This PC influences the nanomaterial's surface characteristics and may impact their interaction with cells. To determine the biological impact of nanomaterial exposure as well as nanotherapeutic applications, it is necessary to understand PC formation. Utilizing a label-free mass spectrometry-based proteomics approach, we examined the composition of the PC for a set of four silver nanoparticles (AgNPs) including citrate-stabilized and polyvinlypyrrolidone-stabilized (PVP) colloidal silver (20 or 110 nm diameter). To simulate cell culture conditions, AgNPs were incubated for 1 h in Dulbecco's Modified Eagle Medium supplemented with 10% fetal bovine serum, washed, coronal proteins solubilized, and proteins identified and quantified by label-free LC-MS/MS. To determine which attributes influence PC formation, the AgNPs were characterized in both water and cell culture media with 10% FBS. All AgNPs associated a common subset of 11 proteins including albumin, apolipoproteins, keratins, and other serum proteins. 110 nm citrate- and PVP-stabilized AgNPs were found to bind the greatest number of proteins (79 and 85 respectively) compared to 20 nm citrate- and PVP-stabilized AgNPs (45 and 48 respectively), suggesting a difference in PC formation based on surface curvature. While no relationships were found for other protein parameters (isoelectric point or aliphatic index), the PC on 20 nm AgNPs (PVP and citrate) consisted of more hydrophobic proteins compared to 110 nm AgNPs implying that this class of proteins are more receptive to curvature-induced folding and crowding in exchange for an increased hydration in the aqueous environment. These observations demonstrate the significance of electrostatic and hydrophobic interactions in the formation of the PC which may have broad biological and toxicological implications.

Dataset Information

Culture media composition influences patient-derived organoid ability to predict therapeutic responses in gastrointestinal cancers.

Publications

Culture media composition influences patient-derived organoid ability to predict therapeutic responses in gastrointestinal cancers.

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