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Microenvironment-dependent phenotypic changes in a SCID mouse model for malignant mesothelioma
Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska institutet. (Psychoneuroimmunology)
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2013 (English)In: Frontiers in Oncology, ISSN 2234-943X, E-ISSN 2234-943X, Vol. 3, 203- p.Article in journal (Refereed) Published
Abstract [en]

Background and Aims: Malignant mesothelioma is an aggressive, therapy-resistant tumor. Mesothelioma cells may assume an epithelioid or a sarcomatoid phenotype, and presence of sarcomatoid cells predicts poor prognosis. In this study, we investigated differentiation of mesothelioma cells in a xenograft model, where mesothelioma cells of both phenotypes were induced to form tumors in severe combined immunodeficiency mice. Methods: Xenografts were established and thoroughly characterized using a comprehensive immunohistochemical panel, array comparative genomic hybridization (aCGH) of chromosome 3, fluorescent in situ hybridization, and electron microscopy. Results: Epithelioid and sarcomatoid cells gave rise to xenografts of similar epithelioid morphology. While sarcomatoid-derived xenografts had higher growth rates, the morphology and expression of differentiation-related markers was similar between xenografts derived from both phenotypes. aCGH showed a convergent genotype for both xenografts, resembling the original aggressive sarcomatoid cell sub-line. Conclusion: Human mesothelioma xenografts from sarcomatoid and epithelioid phenotypes converged to a similar differentiation state, and genetic analyses suggested that clonal selection in the mouse microenvironment was a major contributing factor. This thoroughly characterized animal model can be used for further studies of molecular events underlying tumor cell differentiation.

Place, publisher, year, edition, pages
2013. Vol. 3, 203- p.
Keyword [en]
SCID mice, epithelioid, sarcomatoid, chromosome 3, mesothelioma, differentiation
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:su:diva-96936DOI: 10.3389/fonc.2013.00203PubMedID: 23951555Local ID: P3064OAI: oai:DiVA.org:su-96936DiVA: diva2:667998
Available from: 2013-11-28 Created: 2013-11-28 Last updated: 2017-12-06Bibliographically approved

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