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Endogenous μ‐opioid peptides modulate immune response towards malignant melanoma
Author(s) -
Boehncke Sandra,
Hardt Katja,
Schadendorf Dirk,
Henschler Reinhard,
Boehncke WolfHenning,
Duthey Beatrice
Publication year - 2011
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2010.01158.x
Subject(s) - immune system , melanoma , endogenous opioid , immunohistochemistry , cancer research , opioid peptide , medicine , opioid , immunology , biology , receptor
Opioids exert major effects not only in the central nervous system but also in immune responses. We investigated the effects of μ‐opioid peptides, secreted by tumor cells, on anti‐tumor immune responses. For this purpose, tumor growth was studied in wild‐type and μ‐opioid receptor–deficient (MOR−/−) mice injected with B16 melanoma cells. The ability of these cells to produce opioids was studied by Western blots in vitro. Finally, biopsy material from human melanomas was investigated by immunohistochemistry for ß endorphin expression. Injection of B16 melanoma cells, producing endogenous ß endorphin, in the flank of MOR−/− mice revealed a profound reduction in tumor growth, paralleled by a significantly higher infiltration of immune cells into the tumors, when compared to tumor growth after injection of B16 melanoma cells into wild‐type mice. Opioids present in B16 cell supernatant significantly reduced the proliferation of normal but not MOR−/− leucocytes. Immunohistochemical analyses of biopsies from human melanoma tissues showed a positive correlation between expression of ß endorphin and tumor progression. Our data provide evidence that μ‐opioid peptides may play a major role in cancer progression by modulating immune response. This finding may have implications for the future optimization of immunointerventions for cancer.