Phenotypes and karyotypes of human malignant mesothelioma cell lines

Our plain-English summary of Phenotypes and karyotypes of human malignant mesothelioma cell lines, by V. Relan, L. Morrison, K. Parsonson, et al (PloS One, 2013).

The study

• Authors: V. Relan, L. Morrison, K. Parsonson, B.E. Clarke, E.E. Duhig, M.N. Windsor, K.S. Matar, R. Naidoo, L. Passmore, E. McCaul, D. Courtney, I.A. Yang, K.M. Fong, R.V. Bowman
• Journal: PloS One
• Published: 2013;8(3):e58132
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant mesothelioma is an aggressive tumour of serosal surfaces most commonly pleura. Characterised cell lines represent a valuable tool to study the biology of mesothelioma. The aim of this study was to develop and biologically characterise six malignant mesothelioma cell lines to evaluate their potential as models of human malignant mesothelioma.

Methods: Five lines were initiated from pleural biopsies, and one from pleural effusion of patients with histologically proven malignant mesothelioma. Mesothelial origin was assessed by standard morphology, Transmission Electron Microscopy (TEM) and immunocytochemistry. Growth characteristics were assayed using population doubling times. Spectral karyotyping was performed to assess chromosomal abnormalities. Authentication of donor specific derivation was undertaken by DNA fingerprinting using a panel of SNPs.

Results: Most of cell lines exhibited spindle cell shape, with some retaining stellate shapes. At passage 2 to 6 all lines stained positively for calretinin and cytokeratin 19, and demonstrated capacity for anchorage-independent growth. At passage 4 to 16, doubling times ranged from 30-72 hours, and on spectral karyotyping all lines exhibited numerical chromosomal abnormalities ranging from 41 to 113. Monosomy of chromosomes 8, 14, 22 or 17 was observed in three lines. One line displayed four different karyotypes at passage 8, but only one karyotype at passage 42, and another displayed polyploidy at passage 40 which was not present at early passages. At passages 5-17, TEM showed characteristic features of mesothelioma ultrastructure in all lines including microvilli and tight intercellular junctions.

Conclusion: These six cell lines exhibit varying cell morphology, a range of doubling times, and show diverse passage-dependent structural chromosomal changes observed in malignant tumours. However they retain characteristic immunocytochemical protein expression profiles of mesothelioma during maintenance in artificial culture systems. These characteristics support their potential as in vitro model systems for studying cellular, molecular and genetic aspects of mesothelioma.

In plain English

This laboratory study, from The Prince Charles Hospital in Brisbane, Australia, described six new mesothelioma cell lines. They were grown from tumour samples of six men aged 59 to 86 with malignant mesothelioma: five from pleural biopsies and one from pleural fluid. The article did not study or report the donors' asbestos exposure. All six lines stained positive for two mesothelial markers, calretinin and cytokeratin 19. Under the electron microscope they showed features typical of mesothelioma, such as microvilli and tight junctions between cells. All six formed colonies in soft agar, a sign of tumour-like growth. The time for the cell count to double was reported as between 30 and 72 hours. Five lines were examined for chromosome changes; the sixth could not be. All five had chromosome abnormalities, and three carried only one copy of chromosome 17. Two lines were retested after long culture. In one, four different chromosome patterns narrowed to one. The other gained extra sets of chromosomes. The authors concluded that these characteristics support the lines' potential as laboratory models for studying mesothelioma.

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 characterising human malignant mesothelioma cell lines
• Who was studied: Six cell lines from six male patients aged 59 to 86 with malignant mesothelioma at The Prince Charles Hospital, Brisbane, Australia. Five lines came from pleural biopsies and one from pleural fluid. Tumour types were desmoplastic (1), biphasic (3), epithelioid (1) and unclassified (1).
• Exposure: Not studied; the article does not report the donors' asbestos exposure or fiber types
• Main results:
  • Cells from all six lines stained positively for calretinin and cytokeratin 19 at early passages (p2 to p5)
  • Electron microscopy of all six lines showed features typical of mesothelioma, including microvilli and tight intercellular junctions
  • Microvilli in the cultured cells were shorter overall than those seen in tissue samples of mesothelioma
  • Doubling times across the six lines were reported as ranging from 30 to 72 hours
  • All lines formed colonies in soft agar
  • A single copy of chromosome 17 was found in three lines (MM04, MM05, PF1038)
  • One line (MM13) could not be karyotyped
  • Line MM04 showed four distinct karyotypes at early passage but only one at late passage. Line MM05 developed polyploidy at late passage.
  • DNA fingerprinting matched four of the lines (MM04, MM05, MM13, MM1081) to their donors' blood
• The authors' conclusion: The authors concluded that the characteristics of these six lines support their potential as in vitro models for studying cellular, molecular and genetic aspects of mesothelioma
• Limitations the authors state:
  • Only two immunocytochemical markers were used; the authors note that a wider panel would give fuller characterisation

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Serosal Surface, Pleura, Mesothelioma, Pleural Effusion, Transmission Electron Microscopy (TEM), Authentication, Spindle Cell.

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