Ex vivo model of non‑small cell lung cancer using mouse lung epithelial cells

Sato, Taku; Morita, Mami; Tanaka, Ryota; Inoue, Yui; Nomura, Miyuki; Sakamoto, Yohei; Miura, Koh; Ito, Shigemi; Sato, Iwao; Tanaka, Nobuyuki; Abe, Jiro; Takahashi, Satoshi; Kawai, Masaaki; Sato, Masami; Hippo, Yoshitaka; Shima, Hiroshi; Okada, Yoshinori; Tanuma, Nobuhiro

doi:10.3892/ol.2017.7098

Cited by 18 publications

(19 citation statements)

References 24 publications

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“…Organoids can be subjected to genetic engineering by viral introduction of shRNA and cDNA. With highly efficient lentiviral gene transduction into murine organoids [87], we demonstrated that the whole processes of multi-step carcinogenesis could be recapitulated for the intestine, lungs and the biliary tract, as subcutaneous tumors in nude mice [88,89,90]. Essentially similar results to earlier in vivo studies were obtained in a significantly shorter period of time, suggesting that this approach might at least partly substitute and complement the conventional gene-targeting approach in modeling carcinogenesis.…”

Section: Patient-derived Cellsmentioning

confidence: 99%

Current Status of Patient-Derived Ovarian Cancer Models

Maru

Hippo

2019

Cells

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Ovarian cancer (OC) is one of the leading causes of female cancer death. Recent studies have documented its extensive variations as a disease entity, in terms of cell or tissue of origin, pre-cancerous lesions, common mutations, and therapeutic responses, leading to the notion that OC is a generic term referring to a whole range of different cancer subtypes. Despite such heterogeneity, OC treatment is stereotypic; aggressive surgery followed by conventional chemotherapy could result in chemo-resistant diseases. Whereas molecular-targeted therapies will become shortly available for a subset of OC, there still remain many patients without effective drugs, requiring development of groundbreaking therapeutic agents. In preclinical studies for drug discovery, cancer cell lines used to be the gold standard, but now this has declined due to frequent failure in predicting therapeutic responses in patients. In this regard, patient-derived cells and tumors are gaining more attention in precise and physiological modeling of in situ tumors, which could also pave the way to implementation of precision medicine. In this article, we comprehensively overviewed the current status of various platforms for patient-derived OC models. We highly appreciate the potentials of organoid culture in achieving high success rate and retaining tumor heterogeneity.

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Section: Patient-derived Cellsmentioning

confidence: 99%

Current Status of Patient-Derived Ovarian Cancer Models

Maru

Hippo

2019

Cells

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“…Histologically, tumor glands were densely packed, while disrupted glands were rarely observed, suggestive of anti‐apoptotic effects by Kras G12D . Our experience in organoid‐based tumorigenesis for the lung, pancreas (Matsuura et al, submitted ) and hepato‐biliary tract (Ochiai et al, submitted ) suggests that emergence of a cystic component is closely associated with Kras G12D . Accordingly, future classification of the nodules might as well include “cyst” in the category of non‐tumorous nodules.…”

Section: An Organoid‐based Carcinogenesis Model For Murine Intestinementioning

confidence: 99%

Shortcuts to intestinal carcinogenesis by genetic engineering in organoids

Maru

Onuma

Ochiai³

et al. 2019

Cancer Science

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Inactivation of the Adenomatous polyposis coli (APC) gene is an initiating and the most relevant event in most sporadic cases of colorectal cancer, providing a rationale for using Apc‐mutant mice as the disease model. Whereas carcinogenesis has been observed only at the organism level, the recent development of the organoid culture technique has enabled long‐term propagation of intestinal stem cells in a physiological setting, raising the possibility that organoids could serve as an alternative platform for modeling colon carcinogenesis. Indeed, it is demonstrated in the present study that lentivirus‐based RNAi‐mediated knockdown of Apc in intestinal organoids gave rise to subcutaneous tumors upon inoculation in immunodeficient mice. Reconstitution of common genetic aberrations in organoids resulted in development of various lesions, ranging from aberrant crypt foci to full‐blown cancer, recapitulating multi‐step colorectal tumorigenesis. Due to its simplicity and utility, similar organoid‐based approaches have been applied to both murine and human cells in many investigations, to gain mechanistic insight into tumorigenesis, to validate putative tumor suppressor genes or oncogenes, and to establish preclinical models for drug discovery. In this review article, we provide a multifaceted overview of these types of approaches that will likely accelerate and advance research on colon cancer.

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“…To date, it has been applied to various research fields, including infectious disease models, developmental biology, and epithelial regeneration . We also reported the establishment of murine organoid‐based carcinogenesis models for intestine, lung, hepatobiliary tract, and pancreas . These organoid culture techniques have now become common for patient‐derived samples from diverse types of cancer, which revealed that tumor‐derived organoids basically retained the morphology and genetic aberrations of the original tumors .…”

Section: Introductionmentioning

confidence: 99%

Establishment and characterization of patient‐derived organoids from a young patient with cervical clear cell carcinoma

et al. 2019

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Cervical clear cell carcinoma (cCCC) constitutes an extremely rare subtype of cervical cancer. Consequently, its pathogenesis remains largely unknown, with no cell lines established from primary tumors. Here, we report the first establishment of cCCC organoids, from biopsy samples of a 23‐year‐old patient diagnosed with cCCC. By applying a protocol that we recently optimized for gynecological tumors, we were able to propagate a patient‐derived cell line (PDC) for more than 6 months as organoids. This PDC tolerated cryopreservation and proliferated either as spheroids or adherent cells, and developed xenografts in immunodeficient mice, ensuring robust utility as a cell line. Intriguingly, the resected tumor focally contained serous carcinoma (SC) in a tiny protruding lesion. Both organoids and derivative xenografts resembled the CCC component of the original tumor in histology, immunostaining profile, and genome‐wide copy number changes, including focal gain of MET. Genomic analysis revealed that both organoids and the CCC component harbored only a few mutations, of which 2 mutations were shared in common. In contrast, the SC component showed a mutator‐phenotype and prominent genome instability along with biallelic inactivation of TP53, but none of them were found in organoids or the CCC component. The PDC proved sensitive to major chemotherapeutic agents and MET inhibitors. These observations clearly indicated that the PDC, designated as YMC7, can be used as a novel cCCC cell line and provide novel insights into the pathogenesis of mixed cervical adenocarcinoma. As a valuable resource for rare cancer, it will likely contribute to investigations in many fields.

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Ex vivo model of non‑small cell lung cancer using mouse lung epithelial cells

Cited by 18 publications

References 24 publications

Current Status of Patient-Derived Ovarian Cancer Models

Current Status of Patient-Derived Ovarian Cancer Models

Shortcuts to intestinal carcinogenesis by genetic engineering in organoids

Establishment and characterization of patient‐derived organoids from a young patient with cervical clear cell carcinoma

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