Morphine modulates interleukin-4 or breast cancer cell induced prometastatic activation of macrophages
Immunotherapy: Open Access

Immunotherapy: Open Access
Open Access

ISSN: 2471-9552

Morphine modulates interleukin-4 or breast cancer cell induced prometastatic activation of macrophages

International Conference on Tumor & Cancer Immunology and Immunotherapy

July 28-30, 2016 Melbourne, Australia

Samira Khabbazi, Marie-Odile Parat and Yannick Goumon

University of Queensland, Australia
Centre National de la Recherche Scientifique, France
University of Strasbourg, France

Posters & Accepted Abstracts: Immunother Open Acc

Abstract :

Interactions between cancer cells and stromal cells in the tumor 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 tumor aggressiveness. Opioids are able to modulate tumor growth and metastasis. We tested whether morphine modulates the activation of macrophages induced by interleukin-4 (IL-4), the prototypical M2 polarization inducing cytokine or co-culture 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 methyl naltrexone 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 was 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 tumor aggressiveness by regulating macrophage protease production and M2 polarization within the tumor microenvironment.

Biography :

Email: [email protected]