Establishment and characterization of prostate organoids from treatment-naïve patients with prostate cancer

Abstract

Three-dimensional (3D) organoid culture systems are emerging as potential reliable tools to investigate basic developmental processes of human disease, especially cancer. The present study used established and modified culture conditions to report successful generation and characterization of patient-derived organoids from fresh primary tissue specimens of patients with treatment-naïve prostate cancer (PCa). Fresh tissue specimens were collected, digested enzymatically and the resulting cell suspensions were plated in a 3D environment using Matrigel as an extracellular matrix. Previously established 12-factor medium for organoid culturing was modified to create a minimal 5-factor medium. Organoids and corresponding tissue specimens were characterized using transcriptomic analysis, immunofluorescent analysis, and immunohistochemistry. Furthermore, patient-derived organoids were used to assess the drug response. Treatment-naïve patient-derived PCa organoids were obtained from fresh radical prostatectomy specimens. These PCa organoids mimicked the heterogeneity of corresponding parental tumor tissue. Histopathological analysis demonstrated similar tissue architecture and cellular morphology, as well as consistent immunohistochemical marker expression. Also, the results confirmed the potential of organoids as an in vitro model to assess potential personalized treatment responses as there was a differential drug response between different patient samples. In conclusion, the present study investigated patient-derived organoids from a cohort of treatment-naïve patients. Derived organoids mimicked the histological features and prostate lineage profiles of their corresponding parental tissue and may present a potential model to predict patient-specific treatment response in a pre-clinical setting. © 2022 Spandidos Publications. All rights reserved.

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3d culture, Organoid, Prostate cancer, Stem cells, Treatment response, 4 (2 hydroxyethyl) 1 piperazineethanesulfonic acid, 4',6 diamidino 2 phenylindole, Ab224799, Ab52615, Acetylcysteine, Alcohol, Alpha6 integrin, Aluminum, Amphotericin b, Androgen receptor, Androstanolone, Antiandrogen, Bicalutamide, Bovine serum albumin, Buffer, Carbon dioxide, Cell marker, Chloroform, Citric acid, Collagen type 2, Collagenase, Cytokeratin 8, Dimethyl sulfoxide, Distilled water, Docetaxel, Enzalutamide, Eosin, Fibroblast growth factor 10, Fibroblast growth factor 2, Formaldehyde, Gentamicin, Growth factor, Hematoxylin, Hermes antigen, Immunoglobulin g, Liquid nitrogen, Matrigel, Messenger rna, Methanol, Microrna, Nicotinamide, Noggin, Paraffin, Paraformaldehyde, Penicillin derivative, Peroxidase, Phosphate buffered saline, Polymer, Polysorbate 20, Prostaglandin e2, Prostate specific antigen, Protein p63, Rho kinase, Rho kinase inhibitor, Sc281642a, Sodium chloride, Streptomycin, Transcription factor erg, Transcription factor ets, Triton x 100, Trypan blue, Tumor marker, Vimentin, Adult, Aged, Antigen retrieval, Article, Bioinformatics, Cancer diagnosis, Cancer staging, Cancer tissue, Cell count, Cell culture, Cell cycle, Cell differentiation, Cell lineage, Cell proliferation, Cell suspension, Cell viability, Centrifugation, Confocal laser scanning microscopy, Controlled study, Dehydration, Dna microarray, Drug response, Extracellular matrix, Fetal bovine serum, Follow up, Gene expression, Gene ontology, Histology, Histopathology, Human, Human tissue, Immunofluorescence, Immunohistochemistry, Incubation time, Keratinization, Keratinocyte, Major clinical study, Male, Microscopy, Middle aged, Needle biopsy, Oncogene c myc, Paraffin embedding, Principal component analysis, Prostate adenocarcinoma, Prostatectomy, Rna extraction, Rna isolation, Rna sequence, Room temperature, Signal transduction, Spectrophotometry, Staining, Tissue culture, Tissue section, Transcriptomics, X ray

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