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 journalArticle

30 Citations (Scopus)

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 - Jan 1 2014
Externally publishedYes

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Morphine
Leukocytes
Growth
Lewis Lung Carcinoma
Neoplasms
Conditioned Culture Medium
Placebos
Transendothelial and Transepithelial Migration
Polyvinyl Alcohol
Porifera
Opioid Receptors
Pain Management
Immunosuppressive Agents
Electric Impedance
Knockout Mice
Therapeutics

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Morphine inhibits migration of tumor-infiltrating leukocytes and suppresses angiogenesis associated with tumor growth in mice. / Koodie, Lisa; Yuan, Hongyan; Pumper, Jeffery A.; Yu, Haidong; Charboneau, Richard; Ramakrishnan, Sundaram; Roy, Sabita.

In: American Journal of Pathology, Vol. 184, No. 4, 01.01.2014, p. 1073-1084.

Research output: Contribution to journalArticle

Koodie, Lisa ; Yuan, Hongyan ; Pumper, Jeffery A. ; Yu, Haidong ; Charboneau, Richard ; Ramakrishnan, Sundaram ; Roy, Sabita. / Morphine inhibits migration of tumor-infiltrating leukocytes and suppresses angiogenesis associated with tumor growth in mice. In: American Journal of Pathology. 2014 ; Vol. 184, No. 4. pp. 1073-1084.
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