Endogenous μ-opioid peptides modulate immune response towards malignant melanoma
Endogenous μ-opioid peptides modulate immune response towards malignant melanoma
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DOI：
10.1111/j.1600-0625.2010.01158.x
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发表时间：
2011-01-01
影响因子：
3.6
通讯作者：
Duthey, Beatrice
中科院分区：
文献类型：
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作者：
Boehncke, Sandra;Hardt, Katja;Duthey, Beatrice
阿片类药物不仅在中枢神经系统中发挥重要作用，而且在免疫反应中也发挥重要作用。我们研究了肿瘤细胞分泌的μ阿片肽对抗肿瘤免疫反应的影响。为此，在注射B16黑色素瘤细胞的野生型和μ-阿片受体缺陷（莫尔-/-）小鼠中研究肿瘤生长。这些细胞产生阿片类物质的能力通过体外Western印迹法进行了研究。最后，从人类黑色素瘤活检材料进行了研究，通过免疫组织化学的ss内啡肽的表达。在莫尔-/-小鼠的侧腹注射产生内源性β内啡肽的B16黑色素瘤细胞，与将B16黑色素瘤细胞注射到野生型小鼠中后的肿瘤生长相比，显示出肿瘤生长的显著减少，同时免疫细胞向肿瘤中的浸润显著增加。B16细胞上清液中存在的阿片样物质显著降低正常白细胞的增殖，但不降低莫尔-/-白细胞的增殖。免疫组织化学分析显示，从人类黑色素瘤组织活检的表达，β内啡肽和肿瘤进展之间呈正相关。我们的数据提供的证据表明，μ-阿片肽可能通过调节免疫反应在癌症进展中发挥重要作用。这一发现可能对未来癌症免疫干预的优化具有影响。
Opioids exert major effects not only in the central nervous system but also in immune responses. We investigated the effects of mu-opioid peptides, secreted by tumor cells, on anti-tumor immune responses. For this purpose, tumor growth was studied in wild-type and mu-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 mu-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.