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Experimental metastasis correlates with cyclic AMP accumulation in B16 melanoma clones

Nature volume 308, pages 544–547 (1984)Cite this article

Abstract

Metastasis is a complex process whereby tumour cells from a primary neoplastic growth disseminate throughout the body and establish secondary tumour foci in distant organs. Biochemical traits associated with, or essential for, the expression of the metastatic phenotype have not yet been identified1,2. In the course of examining stimulation of the B16 murine melanoma adenylate cyclase by melanocyte-stimulating hormone (MSH) and by the diterpene forskolin, we noted that tumour cell clones3–5 isolated from common parent cell populations differed widely in their responses to these agonists. We report here that the accumulation of cyclic AMP induced by MSH or forskolin shows a strong positive correlation with the ability of B16 melanoma clones to form pulmonary tumour colonies when injected intravenously (i.v.) into syngeneic mice (‘experimental metastasis’). In parallel in vitro analyses of cyclic AMP metabolism and in vivo assays of experimental metastasis using replicate cell preparations, highly metastatic tumour cell clones consistently show greater than a 30-fold increase in cellular cyclic AMP when exposed to MSH or forskolin. By contrast, clones with limited metastatic abilities respond to the same agonists with only a two- to threefold increase in cellular cyclic AMP. These data suggest that cyclic AMP metabolism is linked with biochemical pathways that are responsible for the formation of experimental metastasis by the B16 melanoma.

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Authors and Affiliations

  1. Department of Tumor Biology, Smith, Kline & French Laboratories, 1500 Spring Garden Street, Philadelphia, Pennsylvania, 19101, USA

    J. R. Sheppard, Thomas P. Koestler, Steven P. Corwin, Charles Buscarino, John Doll, Bruce Lester, Russell G. Greig & George Poste

  2. Dight Institute of Human Genetics, University of Minnesota, 400 Church Street SE, Minneapolis, Minnesota, 55455, USA

    J. R. Sheppard

Authors
  1. J. R. Sheppard
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  2. Thomas P. Koestler
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  3. Steven P. Corwin
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  4. Charles Buscarino
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  5. John Doll
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  7. Russell G. Greig
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Sheppard, J., Koestler, T., Corwin, S. et al. Experimental metastasis correlates with cyclic AMP accumulation in B16 melanoma clones. Nature 308, 544–547 (1984). https://doi.org/10.1038/308544a0

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