Morphine Modulates Interleukin-4- or Breast Cancer Cell-induced Pro-metastatic Activation of Macrophages.
Fiche publication
Date publication
juin 2015
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GOUMON Yannick
Tous les auteurs :
Khabbazi S, Goumon Y, Parat MO
Lien Pubmed
Résumé
Interactions between cancer cells and stromal cells in the tumour microenvironment play a key role in the control of invasiveness, metastasis and angiogenesis. Macrophages display a range of activation states in specific pathological contexts and alternatively activated (M2) macrophages can promote tumour aggressiveness. Opioids are able to modulate tumour growth and metastasis. We tested whether morphine modulates the activation of macrophages induced by (i) interleukin-4 (IL-4), the prototypical M2 polarization-inducing cytokine, or (ii) coculture with breast cancer cells. We showed that IL-4 causes increased MMP-9 production and expression of the alternative activation markers arginase-1 and MRC-1. Morphine prevented IL-4-induced increase in MMP-9 in a naloxone- and methylnaltrexone-reversible fashion. Morphine also prevented IL-4-elicited alternative activation of RAW264.7 macrophages. Expression of MMP-9 and arginase-1 were increased when RAW264.7 were subjected to paracrine activation by 4T1 cells, and this effect was prevented by morphine via an opioid receptor-mediated mechanism. Morphine further decreased 4T1 breast cancer cell invasion elicited by co-culture with RAW264.7. Reduction of MMP-9 expression and alternative activation of macrophages by morphine was confirmed using mouse bone marrow-derived macrophages. Taken together, our results indicate that morphine may modulate tumour aggressiveness by regulating macrophage protease production and M2 polarization within the tumour microenvironment.
Mots clés
Animals, Arginase, genetics, Bone Marrow Cells, drug effects, Cell Differentiation, Cell Line, Cell Line, Tumor, Cell Movement, drug effects, Coculture Techniques, Female, Gene Expression Regulation, Neoplastic, Humans, Interleukin-4, pharmacology, Macrophage Activation, drug effects, Macrophages, cytology, Mammary Glands, Animal, metabolism, Matrix Metalloproteinase 9, genetics, Membrane Glycoproteins, genetics, Mice, Mice, Inbred C57BL, Morphine, pharmacology, Naloxone, pharmacology, Naltrexone, analogs & derivatives, Quaternary Ammonium Compounds, pharmacology, Receptors, Cell Surface, genetics, Signal Transduction
Référence
Sci Rep. 2015 Jun 16;5:11389