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Establishment and Characterization of Novel Patient-Derived Cancer Cell Line

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A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Clinical Medicine, Cell, and Organism Physiology".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 16827

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Special Issue Editors

Dr. Yuki Yoshimatsu

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Guest Editor

Division of Rare Cancer Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Interests: paient-derived cancer model; rare cancer research; sarcoma; expanded indication; biobank; viral carcinogenesis; transcriptomics; exosome/miRNA; tissue culture; primary culture

Dr. Tadashi Kondo

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Guest Editor

Division of Rare Cancer Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Interests: rare cancer research; sarcoma; biobank; precision medicine; biomarker development; target discovery; patient-derived cancer model; proteogenomics; proteomics; bioinformatics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Patient-derived cancer cell lines have facilitated fundamental progress in cancer biology and revolutionized medicine. They enable functional studies of novel genes and proteins, allow the evaluation of anti-tumor effects of novel anti-cancer agents in a high-throughput manner, and provide insights into molecular mechanisms underlying the malignant behavior of cancer cells. The advent of genomics has identified a large number of intriguing genes, and such cell lines are required to interpret their functional properties and the significance of their aberrant regulation in the clinical tumors. The utility of cell lines has been widely recognized, and they have been deposited in cell banks to be shared with the research community. Although cell lines are important tools in cancer research, several critical issues remain to be addressed to improve their utility and possible applications. For example, according to cell line databases, such as Cellosaurus, only a limited number of cell lines have been established for any given cancer; moreover, for a considerable number of cancers, especially rare cancers, no cell lines have been established. Considering the heterogeneity of tumor tissues and the tissue-independence of gene function, we need to expand the collection of cell lines and share them with the research community.

The Special Issue will highlight the establishment and characterization of novel cell lines using clinical materials. Original contributions related to novel cell lines, characterization of novel and existing cell lines, technical notes for cell line establishment and application, and review articles of relevant topics are invited for publication in this Special Issue.

Dr. Yuki Yoshimatsu
Dr. Tadashi Kondo
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Personalized Medicine is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Patient-derived cancer model
Cell line
Primary culture
Precision medicine
Therapeutic target
Biomarker

Published Papers (6 papers)

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Research

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10 pages, 2983 KiB

Open AccessArticle

Establishment and Characterization of MUi027-A: A Novel Patient-Derived Cell Line of Polycystic Kidney Disease with PKD1 Mutation

by Aung Khine Linn, Warun Maneepitasut, Alisa Tubsuwan, Narisorn Kitiyanant, Bunyong Phakdeekitcharoen, Suparerk Borwornpinyo, Suradej Hongeng and Phetcharat Phanthong

J. Pers. Med. 2022, 12(5), 766; https://doi.org/10.3390/jpm12050766 - 09 May 2022

Cited by 3 | Viewed by 1892

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most prevalent genetic diseases affecting the kidneys. A genetically specific mutation model is required to comprehend its pathophysiology and to develop a drug treatment. In this study, we successfully developed human induced pluripotent stem cells (hiPSCs) named MUi027-A from skin fibroblasts of a patient diagnosed with ADPKD and carrying the PKD1 frameshift mutation (c.7946_7947delCT). MUi027-A cells showed the same genetic fingerprints as the parental cells, including the presence of the PKD1 mutation. MUi027-A hiPSCs displayed embryonic stem cell-like characteristics with the capability of differentiating into the three germ layers. Upon directed differentiation, MUi027-A hiPSCs could be differentiated into tubular organoids with the expression of renal cell markers. Furthermore, we compared the efficiency of cyst formation in two human iPSC lines with different PKD1 mutations. When cyst formation was induced by either forskolin or blebbistatin, MUi027-A hiPSC-derived kidney organoids displayed higher frequencies of cyst formation when compared to organoids generated from an iPSC cell line with non-truncating PKD1 mutation genotype (c.5878C > T), suggesting the presence of physiological differences in the mechanism of cyst formation between different PKD1 mutants. Overall, we generated and characterized a novel human iPSC line with a specific PKD mutation and demonstrated its potential as a disease model to study the pathophysiology of genetic determinants in the development of ADPKD disease. Full article

(This article belongs to the Special Issue Establishment and Characterization of Novel Patient-Derived Cancer Cell Line)

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15 pages, 6169 KiB

Open AccessArticle

Establishment and Characterization of NCC-DDLPS4-C1: A Novel Patient-Derived Cell Line of Dedifferentiated Liposarcoma

by Ryuto Tsuchiya, Yuki Yoshimatsu, Rei Noguchi, Yooksil Sin, Takuya Ono, Taro Akiyama, Takeshi Hirose, Shintaro Iwata, Akihiko Yoshida, Seiji Ohtori, Akira Kawai and Tadashi Kondo

J. Pers. Med. 2021, 11(11), 1075; https://doi.org/10.3390/jpm11111075 - 24 Oct 2021

Cited by 3 | Viewed by 2249

Abstract

Dedifferentiated liposarcoma (DDLPS) is a highly malignant sarcoma characterized by the co-amplification of MDM2 and CDK4. Although systemic chemotherapy is recommended for unresectable or metastatic cases, DDLPS is insensitive to conventional chemotherapy, leading to an unfavorable prognosis. Therefore, novel treatment methods are urgently required. Patient-derived cell lines are essential in preclinical studies. Recently, large-scale screening studies using a number of cell lines have been actively conducted for the development of new therapeutic drugs. However, the DDLPS cell line cannot be obtained from public cell banks owing to its rarity, hindering screening studies. As such, novel DDLPS cell lines need to be established. Accordingly, this study aimed to establish a novel DDLPS cell line from surgical specimens. The cell line was named NCC-DDLPS4-C1. NCC-DDLPS4-C1 cells retained copy number alterations corresponding to the original tumors. Further, the cells demonstrated constant growth, spheroid formation, and equivalent invasiveness to MG63 osteosarcoma cells. We also conducted drug screening and integrated the results with those of the previously reported DDLPS cell lines. Consequently, we identified the histone deacetylase inhibitor romidepsin as a novel candidate drug. In conclusion, the NCC-DDLPS4-C1 cell line is a useful tool for the basic study of DDLPS. Full article

(This article belongs to the Special Issue Establishment and Characterization of Novel Patient-Derived Cancer Cell Line)

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Review

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14 pages, 1203 KiB

Open AccessFeature PaperReview

Application of Patient-Derived Cancer Organoids to Personalized Medicine

by Masahiro Shiihara and Toru Furukawa

J. Pers. Med. 2022, 12(5), 789; https://doi.org/10.3390/jpm12050789 - 13 May 2022

Cited by 6 | Viewed by 2755

Abstract

Cell models are indispensable for the research and development of cancer therapies. Cancer medications have evolved with the establishment of various cell models. Patient-derived cell lines are very useful for identifying characteristic phenotypes and susceptibilities to anticancer drugs as well as molecularly targeted therapies for tumors. However, conventional 2-dimensional (2D) cell cultures have several drawbacks in terms of engraftment rate and phenotypic changes during culture. The organoid is a recently developed in vitro model with cultured cells that form a three-dimensional structure in the extracellular matrix. Organoids have the capacity to self-renew and can organize themselves to resemble the original organ or tumor in terms of both structure and function. Patient-derived cancer organoids are more suitable for the investigation of cancer biology and clinical medicine than conventional 2D cell lines or patient-derived xenografts. With recent advances in genetic analysis technology, the genetic information of various tumors has been clarified, and personalized medicine based on genetic information has become clinically available. Here, we have reviewed the recent advances in the development and application of patient-derived cancer organoids in cancer biology studies and personalized medicine. We have focused on the potential of organoids as a platform for the identification and development of novel targeted medicines for pancreatobiliary cancer, which is the most intractable cancer. Full article

(This article belongs to the Special Issue Establishment and Characterization of Novel Patient-Derived Cancer Cell Line)

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12 pages, 2352 KiB

Open AccessEditor’s ChoiceReview

Epithelial and Mesenchymal Features of Pancreatic Ductal Adenocarcinoma Cell Lines in Two- and Three-Dimensional Cultures

by Yuuki Shichi, Fujiya Gomi, Norihiko Sasaki, Keisuke Nonaka, Tomio Arai and Toshiyuki Ishiwata

J. Pers. Med. 2022, 12(5), 746; https://doi.org/10.3390/jpm12050746 - 04 May 2022

Cited by 7 | Viewed by 3307

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an intractable cancer that is difficult to diagnose early, and there is no cure other than surgery. PDAC is classified as an adenocarcinoma that has limited effective anticancer drug and molecular-targeted therapies compared to adenocarcinoma found in other organs. A large number of cancer cell lines have been established from patients with PDAC that have different genetic abnormalities, including four driver genes; however, little is known about the differences in biological behaviors among these cell lines. Recent studies have shown that PDAC cell lines can be divided into epithelial and mesenchymal cell lines. In 3D cultures, morphological and functional differences between epithelial and mesenchymal PDAC cell lines were observed as well as the drug effects of different anticancer drugs. These effects included gemcitabine causing an increased growth inhibition of epithelial PDAC cells, while nab-paclitaxel caused greater mesenchymal PDAC cell inhibition. Thus, examining the characteristics of epithelial or mesenchymal PDAC cells with stromal cells using a 3D co-culture may lead to the development of new anticancer drugs. Full article

(This article belongs to the Special Issue Establishment and Characterization of Novel Patient-Derived Cancer Cell Line)

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15 pages, 1220 KiB

Open AccessReview

Patient-Derived Organoids of Colorectal Cancer: A Useful Tool for Personalized Medicine

by Takumi Kiwaki and Hiroaki Kataoka

J. Pers. Med. 2022, 12(5), 695; https://doi.org/10.3390/jpm12050695 - 26 Apr 2022

Cited by 4 | Viewed by 2957

Abstract

Colorectal cancer is one of the most important malignancies worldwide, with high incidence and mortality rates. Several studies have been conducted using two-dimensional cultured cell lines; however, these cells do not represent a study model of patient tumors very well. In recent years, advancements in three-dimensional culture methods have facilitated the establishment of patient-derived organoids, which have become indispensable for molecular biology-related studies of colorectal cancer. Patient-derived organoids are useful in both basic science and clinical practice; they can help predict the sensitivity of patients with cancer to chemotherapy and radiotherapy and provide the right treatment to the right patient. Regarding precision medicine, combining gene panel testing and organoid-based screening can increase the effectiveness of medical care. In this study, we review the development of three-dimensional culture methods and present the most recent information on the clinical application of patient-derived organoids. Moreover, we discuss the problems and future prospects of organoid-based personalized medicine. Full article

(This article belongs to the Special Issue Establishment and Characterization of Novel Patient-Derived Cancer Cell Line)

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23 pages, 1182 KiB

Open AccessReview

Cell Lines of Circulating Tumor Cells: What Is Known and What Needs to Be Resolved

by Yutaka Shimada, Tetsuo Sudo, Shusuke Akamatsu, Takuro Sunada, Akira Myomoto, Kiyoshi Okano and Kazuharu Shimizu

J. Pers. Med. 2022, 12(5), 666; https://doi.org/10.3390/jpm12050666 - 21 Apr 2022

Cited by 9 | Viewed by 2317

Abstract

The importance of circulating tumor cells (CTC) is well recognized. However, the biological characteristics of CTC in the bloodstream have not yet been examined in detail, due to the limited number of CTC cell lines currently available. Thirty-nine CTC cell lines were reported by 2021. For successful cell culturing, these CTC cell lines were reviewed. Previous studies on short-term cultures of CTC also analyzed approaches for establishing the long-term culture of CTC. Negative selection, hypoxic conditions, three-dimensional conditions, and careful management are preferable for the long-term culture of CTC. However, the establishment of CTC cell lines is dependent on the specific characteristics of each cell type. Therefore, a method to establish CTC cell lines has not yet been developed. Further efforts are needed to resolve this issue. Full article

(This article belongs to the Special Issue Establishment and Characterization of Novel Patient-Derived Cancer Cell Line)

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