Progressive growth of a human pleural mesothelioma xenografted to athymic rats and mice

Abstract

Summary A human malignant pleural mesothelioma was xenografted serially in athymic nude Rowett rats for 27 passages during 33 months. After the two initial passages (P), the take rate during P3-9 was 100% (192/192). The tumour grew progressively during P3-9 in 99% (190/192) and regressed totally in 1% (2/192). The take rate for the tumour xenografted to athymic BALB/c mice was also 100% (17/17) and no regressions were observed. During serial passaging in nude rats, the tumour-volume doubling time (TD) decreased from 6 days in P2 to 3 days in P8-9 (P<0.001) and then remained around 3 days during P10-25. A TD of 11 days in P1 (man-mouse) for tumours grown in mice decreased during 10 passages in rats to 4 days (P<0.005) when the tumour was transplanted to mice in P11. Light microscopic morphology of the tumour was retained in rats and mice. We believe that our experimental tumour model using the nude rat as a carrier of the xenograft will be useful for studies of human mesothelioma.Malignant human pleural mesothelioma (MHPM) is a rare tumour with a poor prognosis. The evaluation of chemoand radiotherapy is difficult in MHPM owing to difficulties in measuring the tumour volume, lack of a generally accepted staging system (Dimitrov et al., 1983) and different prognoses in the three main histologic subtypes of this tumour (Elmes & Simpson, 1976).Growth of human tumour xenografts in athymic nude mice or artificially immunosuppressed mice is regarded as the best currently available experimental model for studying the response of human tumours to drugs (Pihl, 1986). Most human malignant tumours, including pleural mesotheliomas (Chahinian et al., 1980;Linden et al., 1982), have been xenografted to athymic mice.Festing et al. (1978) described an athymic nude rat with an immunodeficiency state comparable to that of the athymic mouse, suggested to be more robust for certain experimental situations, e.g., for experiments requiring surgical manipulations and frequent blood sampling.Experience with the athymic rat is sparse compared to that with the athymic mouse, but many human malignant tumours, including one human malignant pleural mesothelioma (Linden et al., 1982), have been successfully xenografted to rats.In the present study we transplanted another MHPM to both athymic rats and mice and studied the long-term growth pattern of this tumour line in nude rats. We also compared the growth pattern of the tumour in athymic mice and rats. Materials and methods TumourA 66-year old man was found to have an epithelial pleural mesothelioma at thoracoscopic biopsy of the parietal pleura.The tumour was treated with irradiation to a total dose of 40 Gy. About 2 weeks after the completion of the radiotherapy against the diseased hemithorax, an implantation metastasis was noted in the former needle tracks. This tumour nodule was excised and used for establishing this (AKG) tumour cell line. The patient was treated further with 3 courses of combined chemotherapy consisting of doxorubicin and cyclophosphamide, but in spite of this trea...

Microenvironment-Dependent Phenotypic Changes in a SCID Mouse Model for Malignant Mesothelioma

“…A deeper understanding of trans-differentiation between epithelioid and sarcomatoid phenotypes is relevant for the development of therapeutics, and should be taken into consideration when designing in vitro studies and establishing animal models. Mouse models of malignant mesothelioma have been previously described; however, only a few studied the differentiation state of the xenografts (20–22). …”