Morphine inhibits migration of tumor-infiltrating leukocytes and suppresses angiogenesis associated with tumor growth in mice.

Tumor cells secrete factors that stimulate the migration of peripheral blood leukocytes and enhance tumor progression by affecting angiogenesis. In these studies, we investigated the effect of morphine, a known immunosuppressant, on leukocyte migration and recruitment to conditioned media derived from long-term cultures of mouse Lewis lung carcinoma cells. Our results indicate that morphine treatment reduced the migration and recruitment of tumor-infiltrating leukocytes into Matrigel plugs and polyvinyl alcohol sponges containing conditioned media derived from long-term cultures of mouse Lewis lung carcinoma cells when compared with placebo. A reciprocal increase in peripheral blood leukocytes was observed at the time of plug or sponge removal in morphine-treated mice. Decreased angiogenesis was observed in conditioned media derived from long-term cultures of mouse Lewis lung carcinoma cells Matrigel plugs taken from morphine-treated wild-type mice when compared with placebo but was abolished in morphine-treated µ-opioid receptor knockout mice. In addition, in vitro studies using trans-well and electric cell substrate impedance sensing system studies reveal for the first time morphine's inhibitory effects on leukocyte migration and their ability to transmigrate across an activated endothelial monolayer. Taken together, these studies indicate that morphine treatment can potentially decrease leukocyte transendothelial migration and reduce angiogenesis associated with tumor growth. The use of morphine for cancer pain management may be beneficial through its effects on angiogenesis.

Extracellular Vesicles with Exosome-like Features Transfer TLRs between Dendritic Cells.

Accumulating evidence shows that extracellular vesicles (EVs) secreted by immune cells play an important role in intercellular communication. In the current report, we show that EVs released from wild-type bone marrow-derived dendritic cells (BMDCs) transfer TLRs to TLR4-knockout (TLR4KO) BMDCs and increase cellular responsiveness to LPS in recipient cells. The transferred EVs have exosomal characteristics and induce the activation of NF-κB signaling pathways in recipient cells. We further show that BMDC-derived EVs can promote LPS-induced inflammation in TLR4KO mice in vivo. These results indicate that functional TLR4 can be transferred from wild-type to TLR4KO BMDCs through exosome-like EVs.