Journal Article10.1002/IJC.2910470219
Establishment and characterization of five human malignant mesothelioma cell lines derived from pleural effusions
L. S. Manning,Darrel Whitaker,Ashleigh R. Murch,Michael J. Garlepp,Mark R. Davis,Arthur W. Musk,Bruce W. S. Robinson +6 more
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TL;DR: The establishment of 5 human MM cell lines were established from pleural effusions of patients with known crocidolite asbestos exposure, providing an opportunity for comparative study of several aspects of the biology of MM in vitro as well as screening new treatment modalities.
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Abstract: Malignant mesothelioma (MM) is an aggressive tumour of the serosal cavities which is associated with exposure to asbestos. Studies of this tumour have been limited by a paucity of well-characterized human MM cell lines. In this study, 5 human MM cell lines were established from pleural effusions of patients with this malignancy. All 5 patients were males with known crocidolite asbestos exposure, who had received no treatment for their disease and in whom the diagnosis was confirmed by cytology, histology and electron microscopy (EM). These lines have been in culture from 11 to 25 months, and all of them for more than 18 passages. The appearance of the cells in culture was extremely varied; in 3 of the lines they were spindle-shaped with few vacuoles (JU77, LO68 and ONE58); in 1 line they had a thick, stellate shape with vacuoles (NO36) and in 1 they were very pleomorphic in both shape and size with irregular membranes and numerous vacuoles [DeH128 (M)]. Upon reaching confluence, cells in 3 of the 5 lines assumed the cobblestone-like pattern characteristic of epithelial-type cells, whereas in the other 2 (LO68 and ONE58) they remained spindle-shaped. All 5 lines demonstrated a loss of contact inhibition (i.e., piling) at confluence. Minimum doubling times varied significantly from 18 hr (JU77) to more than 30 hr [DeH128 (M)]. Cytological examination showed characteristic mesothelial/mesothelioma morphology, and epithelial membrane antigen (EMA) and cytokeratin were demonstrated in cells from all 5 lines. These cells lacked CEA and epithelial mucin. The presence of cell junctions, glycogen and numerous long, thin, branching microvilli was readily demonstrable by EM. All lines had abnormal karyotypes, with the modal chromosome number varying from 40 to 80. Variable chromosome numbers, numerous structural rearrangements and unrecognizable marker chromosomes were readily observed; however, the only consistent change seen was del 6q21 in 4 of the 5 lines. The establishment of these 5 cultured human MM cell lines now provides an opportunity for comparative study of several aspects of the biology of MM in vitro as well as screening new treatment modalities.
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Citations
Antiproliferative effect of ferrocifen drug candidates on malignant pleural mesothelioma cell lines
TL;DR: Fc-diOH and CDDP were able to upregulate wild type p53 present in MM98 cell line, while Fc-OH-TAM was not, which indicates that, albeit the similar structures, the two ferrocifens exhert different mechanisms of cytotoxicity on MPM cells.
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p53 autoantibodies in patients with malignant mesothelioma: stability through disease progression.
Jenette Creaney,B M McLaren,Sandra Stevenson,Arthur W. Musk,N H de Klerk,Bruce W. S. Robinson,Richard A. Lake +6 more
TL;DR: Results show that anti-p53 antibodies are observed only at a low frequency in the sera of MM patients and where they do occur, their elicitation is an early event that may be unrelated to antigen load.
Auto-antibodies to β-F1-ATPase and vimentin in malignant mesothelioma.
Jenette Creaney,Jenette Creaney,Ian M. Dick,Deborah Yeoman,Sarah Wong,Bruce W. S. Robinson,Bruce W. S. Robinson +6 more
TL;DR: It is demonstrated that vimentin antibody levels were not associated with survival, however high antibody levels to ß-F1-ATPase may be associated with increased survival and this warrants further investigation.
Karyotypic changes in the preclinical and subsequent stages of malignant mesothelioma: A case report
TL;DR: It is concluded that chromosomes 1, 14, 21, and 22 may be involved in the preclinical stage of development of asbestos-induced mesothelioma, whereas the later chromosomal changes may be related to progression of the tumor.
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Use of preclinical models for malignant pleural mesothelioma.
Marie Shamseddin,Joanna Obacz,Mathew J. Garnett,Robert C. Rintoul,Hayley E. Francies,Stefan J. Marciniak +5 more
TL;DR: The most commonly used models of MPM are two-dimensional cell lines established from primary tumours or pleural fluid, and these cell models have significant limitations as discussed by the authors, and newer technologies, such as the tumour-derived organoids, might allow us to address the limitations of existing models and aid in the identification of effective treatments for this challenging-to-treat disease.
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