Heterotransplantation of small‐cell carcinoma of the lung into nude mice: Comparison of intracranial and subcutaneous routes

Abstract

We compared and contrasted intracranial (i.c.) and subcutaneous (s.c.) heterotransplantation of small-cell carcinoma of the lung (SCCL) into athymic nude mice. Fresh human SCCL tumor specimens, tumor colonies grown in soft agarose and continuous cell lines were used. Tumors induced by the three types of specimens were similar, but s.c. and i.c. transplants differed. S.c. tumors had longer latent times, were non-invasive and non-lethal. I.c. tumors has shorter latent periods, invariably grew in the meninges, frequently invaded and destroyed the underlying brain, and were lethal. The tumor-inducing dose for i.c. transplantation was 10 to 1,000 times lower than for s.c. transplantation. Pooled colonies of SCCL tumor specimens grown in soft agarose were inoculated i.c. While they contained relatively small numbers of cells (400-10,000), 83% of these colony specimens induced tumors after 58-243 days, confirming the "stem-cell" origin of the colonies. I.c. and s.c. transplants retained the characteristic morphology of SCCL, and, with one exception, did not metastasize to distant organs. Continuous cell lines could be established readily from both types of transplants, and they retained the characteristic cytology, growth and biochemical properties of the original SCCL tumors. I.c. heterotransplantation of SCCL is a useful tool, especially when small numbers of tumor cells are available, and may provide a model to study the biology and therapy of meningeal carcinomatosis.

Growth of human bronchial carcinomas in nude mice

“…Shorthouse et al (1980) have reported highest take rates for large cell and adenocarcinomas, whereas our success rate was highest with squamous cell carcinomas, however, the differences between the histological types are not significant. Gazdar et al (1981). reported successful heterotransplantation in 13/29 (45%) small cell carcinomas; our success rate was in the same range (6/16; 38% Fogh et al (1980) demonstrated that metastases will grow more readily than will tumours of primary sites.…”

A panel of human lung carcinoma lines: Establishment, properties and common characteristics

“…Our experience with bronchoscopy specimens has shown that they rarely yield sufficient material to allow establishment of a line, and our attempts from fibreoptic bronchoscopy specimens were uniformly unsuccessful. Also of practical benefit was the ease of establishing of cell lines in tissue culture after the tumour line has first been passaged through a murine host, as suggested previously by Gazdar et al (1981a). The established cell lines retained the characteristics of the xenografts from which they were derived, which in turn resembled the patient tumours as far as could be determined (for example, in histological appearance and immunohistochemicBl staining, cell size and chromosomal complement).…”

Reconstituted basement membrane (matrigel) and laminin can enhance the tumorigenicity and the drug resistance of small cell lung cancer cell lines.

“…Human lung cancer cells do not grow readily in athymic mice, even when a large number of cells (>1 x 107 cells per mouse) (21)(22)(23) and/or immunosuppressive agents (22) are used to obtain tumors. Our data demonstrate that low inocula of SCLC cells from both variant and classic cell lines readily form large tumors when coinjected with matrigel in athymic mice.…”