Endogenous μ-opioid peptides modulate immune response towards malignant melanoma

Abstract

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.

Influence of Morphine on Pericyte-Endothelial Interaction: Implications for Antiangiogenic Therapy

“…Clinically used doses of morphine/opioids act on endothelium and tumor cells resulting in tumor progression in vitro and in vivo experimental studies [18, 21, 22, 29–31]. Significantly higher expression of MOR on human lung cancer tissue as compared to nonmalignant tissue in the same organ complements this activity of morphine [21–23].…”

μ-Opioid Receptor Gene A118G Polymorphism Predicts Survival in Patients with Breast Cancer

“…8–11 Activation of μ-opioid receptors in brainstem regions modulates hypothalamic-adrenal-pituitary axis function and increases peripheral glucocorticoids, 12 which may compromise immune function and promote tumor growth. 13,14 Preclinical studies 15,16 and limited human data (reviewed in 17 ) have implicated opioid pathways in the progression of several different types of cancer.…”

Effect of κ-opioid receptor agonist on the growth of non-small cell lung cancer (NSCLC) cells

“…It has been shown that opioids can promote the growth of tumour cells (Lazarczyk et al , 2010). On the other hand, it has been controversially reported that opioids induce the apoptosis of immunocytes, cancer cells and neuroblastoma cells (Boehncke et al , 2010). Thus, it is becoming increasingly recognised that opioids have a role in tumour growth (Saurer et al , 2008).…”