Transplantation of Human Tumors in Nude Mice23

Abstract

Ninety-one human tumors, including various common carcinomas, low-grade malignant tumors, and benign tumors, were transplanted into athymic nude mice. Tumor take was confirmed histologically for 22 neoplasms at the initial transplantation, and 14 serially transplantable tumors were established, including some hitherto unestablished or unreported, such as lung and hepatic cell carcinomas. Among the 91 tumors were 21, 14, and 13 carcinomas of the lung, stomach, and breast, respectively. Transplantability was highest in lung carcinomas (10/21), followed by gastric carcinomas (2/14) and breast carcinomas (1/13). Morphology of original tumors was retained well in most transplanted tumors, but desmoplastic or scirrhous tumors, such as gastric and breast carcinomas, tended to become medullary with a decrease in amount of tumor stroma. The ability to produce mucin in gastric carcinomas or melanin in malignant melanoma was maintained in serially transplantable tumors. In addition, ectopic production of adrenocorticotropin and beta melanocyte-stimulating hormone continued in a transplanted small cell carcinoma of the lung. Preliminary results were obtained on hormone dependency of the transplantable breast carcinoma and on alpha1-fetoprotein in the transplantable hepatic cell carcinoma.

Growth of human bronchial carcinomas in nude mice

“…In our study the overall average doubling time fell from 14.7 days to 7.1 days and remained fairly stable in the succeeding passages. This growth acceleration during the first few transplant generation has also been observed by other workers (Shimosato et al, 1976;Steel et al, 1983). There appeared to be adaptation to growth of tumours in nude mice with succeeding passages.…”

Detection and analysis of mammary gland stem cells

“…A drawback of this assay, at least in its current form, is that it would not distinguish between progenitor cells that have the ability to generate an outgrowth composed solely of terminally differentiated cells versus cells that have the ability to generate outgrowths that contain primitive progenitor cells in addition to terminally differentiated cells. Another potential drawback to this assay is the observation that human breast tumours have a very low engraftment success rate when xenotransplanted subcutaneously or into the fat pads of immune-deficient mice [49][50][51][52][53], For example, in one study where 433 primary human mammary carcinomas were implanted into nude mice, only 28 (6.1%) of the xenotransplants generated successful outgrowths [53]. The highest reported rates of engraftment (>90%) of human tumour fragments into immune-deficient mice have been observed when the tissue is transplanted to highly vascular sites, such as under the renal capsule or intramuscularly [54][55][56].…”

Growth of human gliomas in immune-deficient mice: a possible model for pre-clinical therapy studies

“…Most, but not all, of the tumours which grew initially were transplantable into further hosts, which is the usual experience of those who have been involved with xenograft studies (Shimosato et al, 1976;Berenbaum et al, 1974). The growth rates and histopathological picture of the initial specimens were maintained in subsequent transplants, although future take rates improved in most instances.…”

“…These mice have been shown capable of supporting the growth of many different types of tumour (Rygaard and Povlsen, 1969;Giovanella et al, 1974;Shimosato et al, 1976). All tumours (1-4 pieces per mouse in its seventh passage) implanted into 7 nude mice grew.…”