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Highly Pigmented Human Melanoma Variant Which Metastasizes Widely in Nude Mice, Including to Skin and Brain¹

Division of Cancer and Cell Biology and Department of Pathology, Mount Sinai Hospital Research Institute, Toronto, Ontario, Canada M5G 1X5, and Department of Medical Genetics, University of Toronto, Toronto, Ontario, Canada

The properties of a highly malignant human melanoma variant cell line which metastasizes in nude mice in a tissue-specific pattern are described. The variant, called 70-W, was isolated from the MeWo malignant melanoma by exposure of the latter to stepwise increasing concentrations of the toxic lectin, wheat germ agglutinin. After nine cycles of treatment a population of wheat germ agglutinin-resistant cells was obtained that manifested a 4-fold resistance to wheat germ agglutinin, a property which was found to be stable in culture for over 6 months in the absence of the lectin. Intravenous inoculation of 70-W cells into 4–6-week-old nude mice revealed remarkable differences in metastatic (organ colonization) behavior. Whereas the parent MeWo cells gave rise only to lung metastases, most of which were amelanotic, injection of the 70-W cells resulted in multiple skin (s.c.) and brain and, to a lesser extent, bone marrow, ovarian, mesenteric (gut-associated), muscle, and abdominal metastases all of which were highly melanotic. This is the first report of brain metastases of a human tumor in nude mice. They were found to be bilateral and confined to the deeper layers of the cerebral cortex. The unique malignant behavior of 70-W cells in nude mice should facilitate studies of host and tumor cell factors involved in human melanoma metastasis, melanogenesis, and development of new treatment strategies for disseminated human malignant melanoma.

¹ This work was supported primarily by Grant ROI-CA41233 from the NIH and by a grant from the National Cancer Institute of Canada.

² Present address: The First Department of Oral Surgery, Hokkaido University School of Dentistry, Sapporo 060, Japan.

³ Terry Fox Research Scientist of the National Cancer Institute of Canada. To whom requests for reprints should be addressed.

Received 2/25/88. Revised 5/13/88. Accepted 6/ 1/88.

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