原创力文档crosstalk between chemokine receptor cxcr4 and cannabinoid receptor cb2 in modulating breast cancer growth and invasion趋化因子受体cxcr4和大麻素受体之间的串扰cb2调制乳腺癌生长和入侵.pdfVIP
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crosstalk between chemokine receptor cxcr4 and cannabinoid receptor cb2 in modulating breast cancer growth and invasion趋化因子受体cxcr4和大麻素受体之间的串扰cb2调制乳腺癌生长和入侵
Crosstalk between Chemokine Receptor CXCR4 and
Cannabinoid Receptor CB2 in Modulating Breast Cancer
Growth and Invasion
. .
Mohd W. Nasser , Zahida Qamri , Yadwinder S. Deol, Diane Smith, Konstantin Shilo, Xianghong Zou,
Ramesh K. Ganju*
Department of Pathology and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, United States of America
Abstract
Background: Cannabinoids bind to cannabinoid receptors CB1 and CB2 and have been reported to possess anti-tumorigenic
activity in various cancers. However, the mechanisms through which cannabinoids modulate tumor growth are not well
known. In this study, we report that a synthetic non-psychoactive cannabinoid that specifically binds to cannabinoid
receptor CB2 may modulate breast tumor growth and metastasis by inhibiting signaling of the chemokine receptor CXCR4
and its ligand CXCL12. This signaling pathway has been shown to play an important role in regulating breast cancer
progression and metastasis.
Methodology/Principal Findings: We observed high expression of both CB2 and CXCR4 receptors in breast cancer patient
tissues by immunohistochemical analysis. We further found that CB2-specific agonist JWH-015 inhibits the CXCL12-induced
chemotaxis and wound healing of MCF7 overexpressing CXCR4 (MCF7/CXCR4), highly metastatic clone of MDA-MB-231
(SCP2) and NT 2.5 cells (derived from MMTV-neu) by using chemotactic and wound healing assays. Elucidation of the
molecular mechanisms using various biochemical techniques and confocal microscopy revealed that JWH-015 treatment
inhibited CXCL12-induced P44/P42 ERK activation, cytoskeletal focal adhesion and stress fiber formation, which play a
critical role in breast cancer invasion and metastasis. In
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