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Updated: May 25, 2026
Incorporating Pericytes into an Endothelial Cell Bead Sprouting Assay
Published on: February 16, 2018
Influence of morphine on pericyte-endothelial interaction: implications for antiangiogenic therapy
Kathryn Luk1, Sonja Boatman, Katherine N Johnson
1Vascular Biology Center and Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota Medical School, Mayo Mail Code 480, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
Abstract:
Morphine stimulates tumor angiogenesis and cancer progression in mice. We examined if morphine influences endothelial-pericyte 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 mitogen-activated 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.
Insights
Morphine promotes tumor growth by enhancing blood vessel formation. It stimulates interactions between endothelial and pericyte cells, potentially hindering anti-cancer therapies.
Area of Science:
- Oncology
- Vascular Biology
- Pharmacology
Background:
- Morphine is known to stimulate tumor angiogenesis and cancer progression.
- The precise mechanisms by which morphine influences tumor vascularization remain incompletely understood.
Purpose of the Study:
- To investigate the role of morphine in endothelial-pericyte interaction.
- To elucidate the involvement of platelet-derived growth factor-BB (PDGF-BB) and PDGF receptor-β (PDGFR-β) signaling in morphine-induced angiogenesis.
Main Methods:
- In vitro studies using human umbilical vein endothelial cells and human pericytes exposed to clinically relevant morphine doses.
- In vivo experiments utilizing a transgenic mice model of breast cancer treated with morphine.
- Assessment of PDGF-BB secretion, PDGFR-β activation, and MAPK/ERK phosphorylation.
- Immunohistochemical analysis of pericyte markers (desmin, PDGFR-β) in tumor tissues.
Main Results:
- Morphine stimulated PDGF-BB secretion from endothelial cells.
- Morphine activated PDGFR-β and MAPK/ERK phosphorylation in pericytes.
- In vivo, morphine promoted tumor angiogenesis, pericyte recruitment, and coverage of tumor vessels in a breast cancer model.
- Increased desmin and PDGFR-β immunoreactivity was observed on tumor-associated pericytes.
Conclusions:
- Morphine potentiates endothelial-pericyte interaction through the PDGF-BB/PDGFR-β signaling pathway.
- This interaction promotes tumor angiogenesis and enhances pericyte coverage of tumor vasculature.
- Morphine may potentially compromise the efficacy of antiangiogenic therapies by modulating vascular pericyte function.
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