Establishment and Analysis of Three-Dimensional (3D) Organoids Derived from Patient Prostate Cancer Bone Metastasis Specimens and their Xenografts

Lee, Sang‐Hee; Burner, Danielle; Mendoza, Theresa R; Muldong, Michelle; Arreola, Catalina; Wu, C.; Cacalano, Nicholas A.; Kulidjian, Anna; Kane, Christopher J.; Jamieson, Christina

doi:10.3791/60367-v

Cited by 4 publications

(3 citation statements)

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“…PDXOs overcome some of the limitations of PDXs and are considered "biologically equivalent" or interchangeable due to several key observations. Firstly, they are similar to PDOs, which have been shown to display similar histo-/molecular pathology to the original patient tumors (Calandrini et al, 2020;Sachs et al, 2018;Vlachogiannis et al, 2018;Yao et al, 2020), PDXO and PDX H&E sections demonstrated that each PDXO preserved the histopathology of the parental PDX from different cancers such as lung, colon, gastric, liver, breast, ovarian, and melanoma (Arena et al, 2020;Beshiri et al, 2018;Corso et al, 2019;Guillen et al, 2022;Lee et al, 2020;Schütte et al, 2017;Shi et al, 2020;Xu et al, 2021). Secondly, the genomic DNA and gene expression analysis of PDXO/PDX across these different cancer types showed high concordance.…”

Section: Comparable Histopathology Genomics and Pharmacologymentioning

confidence: 86%

“…We and others have successfully developed PDXOs from PDXs of various cancer types, including NSCLC (non-small cell lung carcinoma), CRC (colorectal carcinoma), gastric carcinoma, pancreatic carcinoma, breast carcinoma, ovarian carcinoma, hepatocellular carcinoma, etc., Table 1 (Arena et al, 2020; Beshiri et al, 2018;Corso et al, 2019;Guillen et al, 2022;Lee et al, 2020;Schütte et al, 2017;Shi et al, 2020;Xu et al, 2021). PDX tumors harvested from mice are enzymatically digested and mechanically disrupted to isolate cells embedded in Matrigel to establish domes in an organoid culture (Xu et al, 2021).…”

Section: Establishing a Biobank Of Matched Organoid And Pdx Modelsmentioning

confidence: 99%

“…The use of extracellular matrices (ECMs) in 3D structures has potentially increased the success rate of PC-derived organoid models by supporting the cellular composition, differentiation ability of epithelial cells, and overall survival (Sato et al, 2011). As a result, PC organoids derived directly from patient tumors have been reported by various groups (Drost et al, 2016;Gao et al, 2014;Lee et al, 2020;Puca et al, 2018;Shenoy et al, 2017) as well as circulating tumor cells from PC patients (CTCs) (Praharaj, Bhutia, Nagrath, Bitting, & Deep, 2018) and also from PDX (Beshiri et al, 2018;Gao et al, 2014;Lee et al, 2020).…”

Section: Prostate Cancer (Pc)mentioning

confidence: 99%

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Translational and Clinical Relevance of PDX‐Derived Organoid Models in Oncology Drug Discovery and Development

Kumari¹,

Li³

2022

Current Protocols

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Patient‐derived cancer disease models conserve many key features of the original human cancers, potentially allowing higher predictive power than traditional cell line models. Accordingly, in vivo patient‐derived xenografts (PDX) are frequently utilized in preclinical and translational oncology studies as patient surrogates for population‐based screens (“mouse clinical trials”), for which large PDX biobanks have been generated over the last decade from various cancer types. In vitro patient‐derived organoids (PDO) have recently emerged as a disruptive technology, enabling early “patient in a dish” clinical trials. Like PDX, PDOs retain the histology/genomics of the original tumor and are highly predictive of the clinical response. Organoids derived from adult stem cells (ASC) in patient tissue can function as mini‐organs. They have greater advantages over other 3D in vitro systems, making them highly predictive, reliable, and consistent in vitro models. Large biobanks enable the adoption of organoids in early drug screening and patient selection. PDX biobanks, as a source of human material, have been used to create 3D in vitro screens, but with limitations. However, creating organoids from the ASCs residing in PDXs has been successfully used as a rapid and cost‐effective way to enable higher throughput in vitro screens and generate matched in vitro/in vivo model pairs that retain genomic, histopathological, and pharmacology profiles. This overview summarizes the generation of matched in vitro/in vivo models from patient material, the advantages over other systems, and the applications to drug discovery. © 2022 Wiley Periodicals LLC.

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Section: Comparable Histopathology Genomics and Pharmacologymentioning

confidence: 86%

Section: Establishing a Biobank Of Matched Organoid And Pdx Modelsmentioning

confidence: 99%

Section: Prostate Cancer (Pc)mentioning

confidence: 99%

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Translational and Clinical Relevance of PDX‐Derived Organoid Models in Oncology Drug Discovery and Development

Kumari¹,

Li³

2022

Current Protocols

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Bone mimetic environments support engineering, propagation, and analysis of therapeutic response of patient-derived cells, ex vivo and in vivo

Paindelli,

Parietti,

Barrios

et al. 2024

Acta Biomaterialia

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Novel Dormancy Mechanism of Castration Resistance in Bone Metastatic Prostate Cancer Organoids

Lee

Mendoza

Burner

et al. 2022

IJMS

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Advanced prostate cancer (PCa) patients with bone metastases are treated with androgen pathway directed therapy (APDT). However, this treatment invariably fails and the cancer becomes castration resistant. To elucidate resistance mechanisms and to provide a more predictive pre-clinical research platform reflecting tumor heterogeneity, we established organoids from a patient-derived xenograft (PDX) model of bone metastatic prostate cancer, PCSD1. APDT-resistant PDX-derived organoids (PDOs) emerged when cultured without androgen or with the anti-androgen, enzalutamide. Transcriptomics revealed up-regulation of neurogenic and steroidogenic genes and down-regulation of DNA repair, cell cycle, circadian pathways and the severe acute respiratory syndrome (SARS)-CoV-2 host viral entry factors, ACE2 and TMPRSS2. Time course analysis of the cell cycle in live cells revealed that enzalutamide induced a gradual transition into a reversible dormant state as shown here for the first time at the single cell level in the context of multi-cellular, 3D living organoids using the Fucci2BL fluorescent live cell cycle tracker system. We show here a new mechanism of castration resistance in which enzalutamide induced dormancy and novel basal-luminal-like cells in bone metastatic prostate cancer organoids. These PDX organoids can be used to develop therapies targeting dormant APDT-resistant cells and host factors required for SARS-CoV-2 viral entry.

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Establishment and Analysis of Three-Dimensional (3D) Organoids Derived from Patient Prostate Cancer Bone Metastasis Specimens and their Xenografts

Cited by 4 publications

References 0 publications

Translational and Clinical Relevance of PDX‐Derived Organoid Models in Oncology Drug Discovery and Development

Translational and Clinical Relevance of PDX‐Derived Organoid Models in Oncology Drug Discovery and Development

Bone mimetic environments support engineering, propagation, and analysis of therapeutic response of patient-derived cells, ex vivo and in vivo

Novel Dormancy Mechanism of Castration Resistance in Bone Metastatic Prostate Cancer Organoids

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