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Loss of lymphocyte cyclic AMP dependent protein kinase activity in malignant melanoma

R A Ortez, E M Hersh, G A Robison

    Journal of Cyclic Nucleotide Research
    |April 1, 1978
    PubMed

    Insights

    Melanoma in mice and humans significantly reduces cyclic AMP dependent protein kinase activity in lymphocytes. This enzyme activity loss, linked to lymphocyte depletion, may be a specific effect of the tumor-bearing state on the immune system.

    Area of Science:

    • Immunology
    • Biochemistry
    • Oncology

    Background:

    • Melanoma is a significant cancer with complex interactions with the immune system.
    • Cyclic AMP dependent protein kinase (PKA) plays a crucial role in cellular signaling and immune function.

    Purpose of the Study:

    • To investigate the impact of melanoma on PKA activity in lymphoid tissues.
    • To explore the relationship between PKA activity, lymphocyte levels, and the tumor-bearing state.

    Main Methods:

    • Assessing PKA activity in thymus, spleen, and lymphocytes of B16 melanoma-bearing mice and human melanoma patients.
    • Measuring cAMP-stimulated calf histone phosphorylation Vmax.
    • Quantifying lymphocyte populations in thymus and spleen.

    Main Results:

    • PKA activity was significantly depressed in the thymus, spleen, and splenic lymphocytes of tumor-bearing mice compared to controls.
    • A similar reduction in PKA activity was observed in peripheral blood lymphocytes of human melanoma patients.
    • The heart showed unaltered PKA activity, suggesting specificity for lymphoid tissues.
    • The decrease in PKA activity correlated with a diminished Vmax for histone phosphorylation.
    • Tumor-bearing mice exhibited a depletion of small lymphocytes in the thymus and spleen.

    Conclusions:

    • Melanoma significantly impairs PKA activity in the lymphoid system, affecting both mice and humans.
    • The observed decrease in PKA activity is likely due to reduced enzyme catalytic efficiency (Vmax).
    • Lymphocyte depletion in tumor-bearing hosts may be mechanistically linked to the observed reduction in PKA activity.

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