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.
Highlights
As previous attempts to passage mesotheliomas or mesothelioma cells in vivo has led to variations in tumour morphology according to passage number
Of the primary mesotheliomas induced with erionite used for the xenografts, two were epithelial, one was sarcomatous and the other four were of mixed morphology
The phenotypic change in XM3 was from a mixed tumour initially with cytokeratin staining of the sporadic epithelial cells at passage 1 (Figure 3) to a completely cytokeratin negative sarcomatous cell tumour at passage 5
Summary
TumoursPleural mesotheliomas were induced in Porton rats (male, not less than 220 g) by intrapleural injection of 20 mg of Oregon erionite. The mesotheliomas from the cell lines were initiated in nude mice by injection of 106 cells subcutaneously, in three mice. Small pieces of tumour (1 mm square) were dissected and implanted subcutaneously on the flanks of three female nude mice under Avertin (tribromoethanol, Aldrich Chemical Co. Ltd., England) anaesthesia. The animals were maintained in a negative pressure isolator until the xenografts had developed to a size of 1-1.5 cm diameter, the mice were culled and autopsied. Representative areas of the tumour and the major organs were fixed as described and examined histologically for metastases. Tumour fragments (1 mm square) were transplanted into four nude mice for subsequent passage and the procedure was repeated for the required number of continuous passages (5-10) for each tumour
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