Implanted Solid Human Tumours Grow Under the Renal Capsule of Cyclosporin‐Immunosuppressed Rats

Abstract

Cyclosporin (CsA) is a potent immunosuppressive drug widely used in organ transplantation. We transplanted fresh surgical samples from human solid malignant tumours into 45 CsA-immunosuppressed rats. Eight out of nine tumour types grew and remained viable for 5 weeks or more in at least two of the transplanted rats. In 29 rats (64%) a distinct growth of primary human tumours was recorded. Five malignancies (intestinal-type gastric carcinoma, adenocarcinoma of the lung, lymph node metastasis of a testicular teratocarcinoma, soft tissue malignant fibrous histiocytoma (MFH), and small-cell sarcoma) showed invasive and progressive growth. In all five cases the largest tumours were 0.9 cm or over in diameter when the rats were killed 5-9 weeks after transplantation. In three cases (adenocarcinoma of the colon, hypernephroma, and a second MFH) the growth of the implants under the kidney capsule was slow, but small living tumour transplants were still found 3-6 weeks later. In every case the microscopic morphology of the xenograft tumour was identical with the original tumour. In two cases the primary xenografts (teratocarcinoma and small-cell sarcoma) were retransplanted into 11 CsA-immunosuppressed rats. In both types the second passage tumours grew, and the take-off and growth rates were comparable to the primary xenografts. Cyclosporin-treated laboratory rats are an alternative to immunodeficient nude and SCID mice for growing fresh human tumour transplants in vivo. Although a few infections were encountered, most of the rats survived the CsA treatment well for up to 2 months.

A cloned human germ cell tumor-derived cell line differentiating in culture

“…After the operation, the animals were immunosuppressed by intraperitoneal administration of 60 mg/kg Cyclosporin A. The treatment was continued by 3 weekly injections of 30 mg/kg Cyclosporin A until the rats were killed 5-7 weeks later (Kaartinen et al, 1994). Tumors were similarly made by transplanting 10 6 cultured cells under the rat kidney capsule (Kaartinen,1988).…”

Visualization of Inflammation at Early Stage of Lung Cancer in Xenografted Temporally Immunosuppression Rats by Ferrioxamine Magnetic Resonance Imaging

“…Therefore, a temporally immunosuppressed animal model that will not reject human cancer cells at the starting period where afterwards a reversible suppressant can be achieved after withdrawal is crucial for understanding the phenomenon. Kaartinen et al [6] and Hoogenhout et al [4] showed that Wistar rats treated with cyclosporin A develop a state of immune suppression that permits the growth of tumor xenografts. It was also demonstrated that in these models there was no alteration in the tumor doubling time or histological morphology of the xenografts in the adapted host when compared to those in the donor tumors.…”

Prolonged Survival of Human Hepatocarcinoma Cells in the Liver of Newborn C57BL/6 Mice and Resulting Cellular Xenorejection, Especially the Activation of Hepatic Natural Killer T Cells

“…Studies performed to elucidate the immune mechanisms of tumor-host interactions in immunocompetent tumor xenograft models will increase our understanding of tumor xenorejection. Previous studies have demonstrated that tumor xenografts can grow in some immunologically privileged sites, such as the anterior chamber of the eye, the hamster cheek pouch, or under the kidney capsule of mice or rats with limited cyclosporine A (CsA) treatment [8,9] . The potential barriers to successful xenograft survival are believed to be T-cell-mediated xenorejection and tissue microenvironments.…”