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Malignant melanoma metastasis to brain: role of degradative enzymes and responses to paracrine growth factors

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Brain Tumor Invasiveness

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Abstract

Mouse and human melanoma cells metastatic to the brain express degradative enzyme activities that are used for invasion of brain basement membrane and parenchyma. Compared to poorly metastatic or lung- or ovary-metastatic murine melanoma lines, the brain-metastatic sublines secreted higher levels of a variety of degradative enzymes. Brain-metastatic murine and human melanoma cells also degraded subendothelial basement membrane and reconstituted basement membrane at rates higher than other metastatic melanoma cells. In some cases these degradative activities in mouse and human melanoma cells can be induced by paracrine factors known to be present in the brain parenchyma, such as nerve growth factor (NGF). NGF stimulates the expression of degradative enzymes, such as the endo-ß-glucuronidase heparanase, that are important in basement membrane penetration but this factor does not stimulate melanoma cell growth. The growth of brain-metastasizing melanoma cells appears to be stimulated by other paracrine growth factors, such as paracrine transferrin. Melanoma cells metastatic to brain express higher numbers of transferrin receptors and respond and proliferate at lower concentrations of transferrin than do melanoma cells metastatic to other sites or poorly metastatic melanoma cells. The results suggest that degradation and invasion of brain basement membrane and responses to paracrine neurotrophins and paracrine transferrins are important properties in brain metastasis of murine and human malignant melanoma cells.

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Author information

Authors and Affiliations

  1. Department of Tumor Biology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas, 77030, USA

    Garth L. Nicolson, John L. Herrmann, David G. Menter, Philip G. Cavanaugh & Dario Marchetti

  2. Laboratory of Biomedical Research, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, 113, Japan

    Motowo Nakajima

  3. Department of Otolaryngology, Kyungpook National University School of Medicine, Taegu, 700-412, Korea

    June Sik Park

Authors
  1. Garth L. Nicolson
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  2. Motowo Nakajima
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  3. John L. Herrmann
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  4. David G. Menter
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  5. Philip G. Cavanaugh
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  6. June Sik Park
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  7. Dario Marchetti
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Editor information

Editors and Affiliations

  1. Pittsburgh Cancer Institute, University of Pittsburgh Medical Center, USA

    Ronald H. Goldfarb

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© 1994 Springer Science+Business Media Dordrecht

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Nicolson, G.L. et al. (1994). Malignant melanoma metastasis to brain: role of degradative enzymes and responses to paracrine growth factors. In: Goldfarb, R.H. (eds) Brain Tumor Invasiveness. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2622-3_6

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  • DOI: https://doi.org/10.1007/978-1-4615-2622-3_6

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6124-4

  • Online ISBN: 978-1-4615-2622-3

  • eBook Packages: Springer Book Archive

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