Influence of morphine on pericyte-endothelial interaction: Implications for antiangiogenic therapy

Kathryn Luk, Sonja Boatman, Katherine N. Johnson, Olivia A. Dudek, Natalie Ristau, Derek Vang, Julia Nguyen, Kalpna Gupta

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Abstract

Morphine stimulates tumor angiogenesis and cancer progression in mice. We examined if morphine influences endothelialpericyte interaction via platelet-derived growth factor-BB (PDGF-BB) and PDGF receptor-β (PDGFR-β). Clinically relevant doses of morphine stimulated PDGF-BB secretion from human umbilical vein endothelial cells and activated PDGFR-β and mitogenactivated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) phosphorylation in human pericytes. These in vitro effects of morphine were translated into promotion of tumor angiogenesis in a transgenic mice model of breast cancer when treated with clinically used dose of morphine. Increased vessel-associated immunoreactivity of desmin and PDGFR-β was observed on pericytes in tumors of morphine-treated mice. These data suggest that morphine potentiates endothelial-pericyte interaction via PDGF-BB/PDGFR-β signaling and promotes tumor angiogenesis, pericyte recruitment, and coverage of tumor vessels. We speculate that morphine may impair the effectiveness of antiangiogenic therapy by influencing vascular pericyte coverage.

Original languageEnglish (US)
Article number458385
JournalJournal of Oncology
DOIs
StatePublished - Feb 6 2012

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