Phenotypic stability and metastatic behaviour of serially xenografted rat mesotheliomas

Our plain-English summary of Phenotypic stability and metastatic behaviour of serially xenografted rat mesotheliomas, by R.E. Edwards, R.J. Hill, D.G. Brown, et al (British Journal of Cancer, 1990).

The study

• Authors: R.E. Edwards, R.J. Hill, D.G. Brown, P. Carthew
• Journal: British Journal of Cancer
• Published: 1990;62(2):201-4
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Mesotheliomas induced in rats by intrapleural injection of the fibrous zeolite, erionite, were serially transplanted in nude mice for up to ten generations. The cell phenotypes (epithelial or sarcomatous) were well maintained during passaging, as determined morphologically and by the expression of the cytokeratin markers demonstrated in normal mesothelial cells. Some of the tumours occasionally produced metastasis in nude mice. In contrast, a cloned epithelial cell mesothelioma and sarcomatous cell mesothelioma, the original cells of which were isolated in tissue culture, both produced regular multiple metastases when passaged in nude mice. These metastases were frequently found on the visceral pleura, rather than in the lung parenchyma, in nude mice. The high metastatic rate of the xenograph mesotheliomas derived by in vitro isolation of cells from mesotheliomas is atypical of the usual behaviour of xenografts of mesotheliomas.

In plain English

This was an animal experiment. Pleural mesotheliomas were induced in male Porton rats by intrapleural injection of 20 mg of Oregon erionite, and pieces of seven such tumours were implanted under the skin of female nude mice and serially passaged for 5 to 10 generations. Two cloned cell lines from a UICC crocidolite-induced rat mesothelioma, the epithelial Carm-12 and the sarcomatous Fibro-2, were also passaged ten times. The authors reported that all xenografts except XM3 kept their phenotype. XM3 changed from a mixed, partly cytokeratin-positive tumour at passage 1 to a cytokeratin-negative sarcomatous tumour at passage 5. However, the article's Table I also lists XM2 as a mixed, partly cytokeratin-positive original tumour whose xenograft was a cytokeratin-negative primitive cell mesothelioma. Metastases from the primary-tumour xenografts were infrequent: four of the seven tumours had metastases, each at only one passage. Carm-12 gave peritoneal metastases at six passages and Fibro-2 at eight. Lung metastases from both tended to lie on the visceral pleura rather than in the parenchyma.

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: Animal experiment: serial subcutaneous xenografting of rat mesotheliomas and mesothelioma cell lines in nude mice, with histology and cytokeratin immunostaining
• Who was studied: Seven erionite-induced pleural mesotheliomas from male Porton rats (two epithelial, one sarcomatous, four mixed) plus two cloned mesothelioma cell lines, nine tumours in total. All were passaged in female nude mice, with three to four mice per tumour per passage, for 5 to 10 passages.
• Exposure: The primary tumours were induced in rats by intrapleural injection of 20 mg Oregon erionite (a fibrous zeolite). The two cloned cell lines came from a UICC crocidolite-induced rat mesothelioma (Me 9).
• Main results:
  • The authors stated in the results text that all xenografts from the primary erionite-induced mesotheliomas except XM3 kept their original phenotype through passaging.
  • XM3 changed from a mixed tumour with cytokeratin-positive epithelial cells at passage 1 to a cytokeratin-negative sarcomatous tumour at passage 5.
  • Table I lists XM2's original tumour as mixed, with cytokeratin staining positive on the epithelium of cystic components. Its xenograft is listed as a primitive cell mesothelioma that was cytokeratin negative.
  • Metastases from the seven primary-tumour xenografts were infrequent: four of the seven tumours metastasised, each at a single passage.
  • Among the three primary-derived xenografts with lung metastases, one had metastases only on the pleura and two had relatively more pleural than parenchymal metastases.
  • The cell-line xenografts metastasised to the peritoneum repeatedly: Carm-12 at six passages, Fibro-2 at eight passages.
  • The authors reported that lung metastases from both cell-line xenografts showed a bias toward the visceral pleura.
  • For Carm-12 xenografts, visceral pleural lung metastases occurred at four passages (six animals in total), compared with lung parenchymal metastases in two animals.
  • For Fibro-2 xenografts, seven passages (10 animals) had pleural metastases, compared with eight animals with parenchymal metastases. Pleural metastases outnumbered parenchymal ones only at passages 4, 5 and 9.
  • Both cell-line derived xenograft types were cytokeratin negative throughout passaging.
  • The two cell-line derived xenografts showed cartilage and bone more often than the xenografts taken directly from primary tumours.
• The authors' conclusion: The authors concluded that, with one exception among the nine tumours, tumour cell phenotype was well preserved for up to ten generations in nude mice, which they said made somatic cell hybridisation unlikely. They described the high metastatic rate of the xenografts derived from cells isolated in culture as atypical for mesothelioma xenografts.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Zeolite, erionite, Mesothelial Cells, Metastasis, Visceral Pleura, Parenchyma.

Related studies

• Progressive growth of a human pleural mesothelioma xenografted to athymic rats and mice — C.J. Lindén, L. Johansson (1988)
• Phenotypic characterisation of peripheral blood lymphoid cells in people exposed to fibrous zeolite — M. Ozesmi, A. Karlsson-Parra, et al. (1986)
• Histology and ultrastructure of serially transplanted rat mesotheliomas — J.C. Wagner, N.F. Johnson, et al. (1982)
• Characterization of human malignant mesothelioma cell lines orthotopically implanted in the pleural cavity of immunodeficient mice for their ability to grow and form metastasis — D. Martarelli, A. Catalano, et al. (2006)
• Extracellular protease imaging for cell mass tracking of xenografted human malignant pleural mesothelioma — L. Zhou, W. El-Deiry, et al. (2012)
• Presence of innate lymphoid cells in pleural effusions of primary and metastatic tumors: Functional analysis and expression of PD-1 receptor — N. Tumino, S. Martini, et al. (2019)

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