Establishment and characterization of NCC-DMM1-C1, a novel patient-derived cell line of desmoplastic malignant pleural mesothelioma

Our plain-English summary of Establishment and characterization of NCC-DMM1-C1, a novel patient-derived cell line of desmoplastic malignant pleural mesothelioma, by R. Noguchi, Y. Yoshimatsu, T. Ono, et al (Oncology Letters, 2022).

The study

• Authors: R. Noguchi, Y. Yoshimatsu, T. Ono, A. Sei, N. Motoi, Y. Yatabe, Y. Yoshida, S. Watanabe, T. Kondo
• Journal: Oncology Letters
• Published: 2022;23(2):64
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Desmoplastic malignant pleural mesothelioma (DMM) is a rare histological variant of malignant pleural mesothelioma, which is a highly aggressive neoplasm of the mesothelium. DMM is associated with distant metastases and short survival. Effective treatments for DMM are not established and the development of histotype-tailored treatments is difficult due to the rarity of the disease. Although patient-derived cancer models are crucial tools for the development of novel therapeutics, they are difficult to obtain for DMM; no DMM cell lines or xenografts are available from public biobanks and only two cell lines have been reported. Thus, the present study aimed to establish a novel cell line of DMM as a resource for drug screening. A cell line of DMM was established, designated as NCC-DMM1-C1, using surgically resected tumor tissues from a 73-year-old male patient with DMM. Characteristics of NCC-DMM1-C1 cells were examined, such as growth, spheroid formation and invasion capability. Drug targets and anti-cancer drugs with anti-proliferative efficacy were examined using a comprehensive kinase activity assay and drug screening of 213 anti-cancer agents, respectively. NCC-DMM1-C1 exhibited fast growth, spheroid formation and invasion capability, suggesting that the NCC-DMM1-C1 cells retained the aggressive features of DMM. NCC-DMM1-C1 cells and the tumor tissue shared common activity profiles of kinases, which included FES, Wee1, platelet-derived growth factor receptor-β and Src. The drug screening revealed that bortezomib, fostamatinib, gemcitabine, homoharringtonine and vinorelbine had anti-proliferative effects, which have not been previously reported for DMM. It was concluded that NCC-DMM1-C1 cells may be a useful tool for the study of DMM.

Copyright: © Noguchi et al.

In plain English

This laboratory study described a new cell line, named NCC-DMM1-C1, grown from tumor tissue surgically removed from one patient with desmoplastic malignant pleural mesothelioma (DMM), a rare form of pleural mesothelioma. The patient was a 73-year-old man treated at the National Cancer Center Hospital in Tokyo. He had been exposed to asbestos from age 25 to 60. The article did not name a fiber type. DNA testing confirmed the cells came from the patient. The cells doubled about every 25.9 hours and formed spheroids. They invaded more than a comparison bone-cancer (MG63) cell line. They carried chromosome 9p deletions that included the CDKN2A gene. Signaling-enzyme (kinase) activity in the cells closely matched the tumor's (r2=0.86). Of 213 cancer drugs screened, bortezomib, gemcitabine, homoharringtonine, fostamatinib and vinorelbine slowed cell growth at concentrations under 100 nM. Two staining markers, D2-40 and WT1, differed between the cells and the tumor. The authors concluded the cell line may be useful in drug development. They noted it comes from a single patient, and that the drug results need confirming in other models before clinical trials.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study establishing and characterizing a patient-derived cell line, including high-throughput drug screening
• Who was studied: One patient, a 73-year-old male with desmoplastic malignant pleural mesothelioma, seen at the National Cancer Center Hospital, Tokyo, Japan; the cell line was grown from his surgically resected tumor tissue
• Exposure: The patient had asbestos exposure from age 25 to 60 years (fiber type and source not stated). In the laboratory, the cells were exposed to 213 anti-cancer agents.
• Main results:
  • DNA (STR) profiling matched the cell line to the patient's tissue at a 100% match ratio, and no Mycoplasma contamination was detected
  • The cell line had a population doubling time of 25.9 hours
  • The cell line's invasion capability was higher than that of MG63 osteosarcoma cells
  • The cells had deletions mostly involving chromosome arm 9p, and the gene cyclin-dependent kinase inhibitor 2A was located in the deleted regions
  • Kinase activity was highly similar between the cell line and the tumor tissue (r2=0.86). Highly phosphorylated peptides in both included FES, Wee1, PDGFR-β and Src.
  • Five agents had IC50 values under 100 nM in the cell line. Per Table II these were vinorelbine 0.04 µM, gemcitabine 0.053 µM, bortezomib 0.055 µM, homoharringtonine 0.072 µM and fostamatinib 0.097 µM.
  • IC50 values were calculated for 13 agents, including four used for DMM. Per Table II, cisplatin had an IC50 of 5.38 µM and pemetrexed disodium hydrate 0.49 µM.
  • Staining for D2-40 and WT1 differed between the cell line and the original tumor tissue
• The authors' conclusion: The authors concluded that they had established a novel DMM cell line and demonstrated its characteristics and its usefulness in high-throughput drug screening. They suggested it may be useful in drug development.
• Limitations the authors state:
  • The results come from only a single cell line; cell lines from other patients are needed
  • The candidate drugs need validation in other patient-derived models, such as organoids and xenografts, before clinical trials
  • Drugs were screened one at a time, not in combinations as used clinically
  • The kinase activities found need validation by other methods, such as western blot

Topics

Medical terms in this study, explained in our Lexicon: Desmoplastic Mesothelioma, Pleural Mesothelioma, Neoplasm, Mesothelium, Platelet-Derived Growth Factor (PDGF), Gemcitabine, Vinorelbine.

Related studies

• Establishment and characterization of five human malignant mesothelioma cell lines derived from pleural effusions — L.S. Manning, D. Whitaker, et al. (1991)
• Establishment and histopathological study of patient-derived xenograft models and primary cell lines of epithelioid malignant peritoneal mesothelioma — Z.R. Yang, Z.G. Chen, et al. (2021)
• Establishment and characterization of 20 human non-small cell lung cancer cell lines in a serum-free defined medium (ACL-4) — N. Masuda, M. Fukuoka, et al. (1991)
• Establishment and characterization of CRISPR/Cas9-mediated NF2-/- human mesothelial cell line: Molecular insight into fibroblast growth factor receptor 2 in malignant pleural mesothelioma — M. Wahiduzzaman, S. Karnan, et al. (2019)
• Establishment and mutation analysis of a novel malignant peritoneal mesothelioma cell line, TU-MM-1, using whole genome sequencing — N. Oumi, H. Itamochi, et al. (2016)
• Establishment and Characterization of Patient-Derived Xenografts (PDXs) of Different Histology from Malignant Pleural Mesothelioma Patients — R. Affatato, P. Mendogni, et al. (2020)

Browse more research in Oncology Letters, or return to medical research.