Modeling Pancreatic Cancer with Patient-Derived Organoids Integrating Cancer-Associated Fibroblasts

Go, Yoon-Ha; Choi, Woo Hee; Bae, Won Jung; Jung, Sook-In; Cho, Chang-Hoon; Lee, Seung Ah; Park, Joon Seong; Ahn, Ji Mi; Kim, Sung Won; Lee, Kyung Jin; Lee, Dakeun; Yoo, Jongman

doi:10.3390/cancers14092077

Cited by 17 publications

(12 citation statements)

References 45 publications

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“…To overcome this limitation, researchers have attempted to incorporate stromal elements in their organoid models. 5 In pancreatic cancer, a coculture model using PDOs and CAFs has been attempted, 6,7 and our group demonstrated that the CAF-integrated pancreatic cancer organoid model could better represent the patient's tumor. 7 These attempts all aim to create a better ex vivo cancer model for precision medicine.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous establishment of pancreatic cancer organoid and cancer‐associated fibroblast using a single‐pass endoscopic ultrasound‐guided fine‐needle biopsy specimen

Kim

Woo

Yang

et al. 2023

Digestive Endoscopy

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Considering the critical roles of cancer‐associated fibroblasts (CAFs) in pancreatic cancer, recent studies have attempted to incorporate stromal elements into organoid models to recapitulate the tumor microenvironment. This study aimed to evaluate the feasibility of patient‐derived organoid (PDO) and CAF cultures by using single‐pass endoscopic ultrasound‐guided fine‐needle biopsy (EUS‐FNB) samples from prospectively enrolled pancreatic cancer patients. The obtained samples were split into two portions for PDO and CAF cultures. PDOs and CAFs were cultured successfully in 54.4% (31/57) and 47.4% (27/57) of the cases, respectively. Both components were established in 21 cases (36.8%). Various clinicopathologic factors, including the tumor size, tumor location, clinical stage, histologic subtype, and tumor differentiation, did not influence the PDO establishment. Instead, the presence of necrosis in tumor samples was associated with initial PDO generation but no further propagation beyond passage 5 (P = 0.024). The “poorly cohesive cell carcinoma pattern” also negatively influenced the PDO establishment (P = 0.018). The higher stromal proportion in tumor samples was a decisive factor for successful CAF culture (P = 0.005). Our study demonstrated that the co‐establishment of PDOs and CAFs is feasible even with a single‐pass EUS‐FNB sample, implying an expanding role of endoscopists in future precision medicine.

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Section: Introductionmentioning

confidence: 99%

Simultaneous establishment of pancreatic cancer organoid and cancer‐associated fibroblast using a single‐pass endoscopic ultrasound‐guided fine‐needle biopsy specimen

Kim

Woo

Yang

et al. 2023

Digestive Endoscopy

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“…A recent study regarding a CAF-integrated PaC organoid model supports that deposited collagen I in the extracellular matrix counteracts the chemotherapeutic effect by blocking drug transport. 34 It is cost-effective and time-saving to use PaC cell lines, serving tumorigenic exploration and therapeutic evaluation in vitro . Yet, there is still a real gap when considering clinical customization.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of Tumorigenicity, Spheroid Niche, and Drug Resistance of Pancreatic Cancer Cells in Three-Dimensional Culture System

Hung,

Mao,

Fan

et al. 2024

J. Cancer

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The three-dimensional (3D) cell culture technique has been applied comprehensively as a variable platform for medical research, biochemical signal pathway analysis, and evaluation of anti-tumor treatment response due to an excellent recapitulation of a tumor microenvironment (TME) in the in vitro cultured cancer cells. Pancreatic cancer (PaC) is one of the toughest malignancies with a complex TME and refractory treatment response. To comprehensively study the TME of PaC, there is an eager need to develop a 3D culture model to decompose the cellular components and their cross interactions. Herein, we establish a 3D PaC culture system with cancer stem cell (CSC) and scalability properties. To validate our model, we tested the individual PaC cell and the combined effects with cancer-associated fibroblasts (CAFs) on cancer tumorigenicity, the cellular interaction through the CXCR3/CXCL10 axis, and cellular responses reflection of anti-cancer treatments. With the help of our 3D technology, a simulated malignant spheroid with important stromal populations and TME physiochemical properties may be successfully recreated. It can be used in a wide range of preclinical research and helpful in advancing basic and translational cancer biology.

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“…The organoid model of pancreatic cancer histologically resembles human pancreatic cancer [ 221 ] with identification of pathways involved in oncology therapy [ 222 ]. Moreover, pancreas organoids were used to study diabetes and other metabolic disorders [ 223 , 224 ].…”

Section: Organoids Modeling Several Diseasesmentioning

confidence: 99%

Revolutionizing Disease Modeling: The Emergence of Organoids in Cellular Systems

Silva-Pedrosa

Salgado

Ferreira

2023

Cells

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Cellular models have created opportunities to explore the characteristics of human diseases through well-established protocols, while avoiding the ethical restrictions associated with post-mortem studies and the costs associated with researching animal models. The capability of cell reprogramming, such as induced pluripotent stem cells (iPSCs) technology, solved the complications associated with human embryonic stem cells (hESC) usage. Moreover, iPSCs made significant contributions for human medicine, such as in diagnosis, therapeutic and regenerative medicine. The two-dimensional (2D) models allowed for monolayer cellular culture in vitro; however, they were surpassed by the three-dimensional (3D) cell culture system. The 3D cell culture provides higher cell–cell contact and a multi-layered cell culture, which more closely respects cellular morphology and polarity. It is more tightly able to resemble conditions in vivo and a closer approach to the architecture of human tissues, such as human organoids. Organoids are 3D cellular structures that mimic the architecture and function of native tissues. They are generated in vitro from stem cells or differentiated cells, such as epithelial or neural cells, and are used to study organ development, disease modeling, and drug discovery. Organoids have become a powerful tool for understanding the cellular and molecular mechanisms underlying human physiology, providing new insights into the pathogenesis of cancer, metabolic diseases, and brain disorders. Although organoid technology is up-and-coming, it also has some limitations that require improvements.

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Modeling Pancreatic Cancer with Patient-Derived Organoids Integrating Cancer-Associated Fibroblasts

Cited by 17 publications

References 45 publications

Simultaneous establishment of pancreatic cancer organoid and cancer‐associated fibroblast using a single‐pass endoscopic ultrasound‐guided fine‐needle biopsy specimen

Simultaneous establishment of pancreatic cancer organoid and cancer‐associated fibroblast using a single‐pass endoscopic ultrasound‐guided fine‐needle biopsy specimen

Enhancement of Tumorigenicity, Spheroid Niche, and Drug Resistance of Pancreatic Cancer Cells in Three-Dimensional Culture System

Revolutionizing Disease Modeling: The Emergence of Organoids in Cellular Systems

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