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

Lisa Koodie, Hongyan Yuan, Jeffery A. Pumper, Haidong Yu, Richard Charboneau, Sundaram Ramakrishnan, Sabita Roy

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1073-1084
Number of pages12
JournalAmerican Journal of Pathology
Volume184
Issue number4
DOIs
StatePublished - Apr 2014

Bibliographical note

Funding Information:
Supported by research funding from National Institute on Drug Abuse grant F31-DA021005-01 and National Institute of Dental and Craniofacial Research grant T32DE007288 (L.K.); CA114340/CA/NCI NIH HHS grant CA114340 (S.Ra.); and National Institute on Drug Abuse grants RO1 DA 12104 , RO1 DA 022935 , RO1 DA031202 , KO2 DA 015349 , and P50 DA 011806 (S.Ro.).

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