Cytochrome P450 epoxygenase promotes human cancer metastasis

Cytochrome P450 (CYP) epoxygenases convert arachidonic acid to four regioisomeric epoxyeicosatrienoic acids (EET), which exert diverse biological activities in a variety of systems. We previously reported that the CYP2J2 epoxygenase is overexpressed in human cancer tissues and cancer cell lines and...

Full description

Saved in:

Bibliographic Details
Published in:	Cancer research (Chicago, Ill.) Ill.), 2007-07, Vol.67 (14), p.6665-6674
Main Authors:	JIANG, Jian-Gang, NING, Yao-Gui, CARD, Jeffrey W, JIANING WANG, ZEIDIN, Darryl C, DAO WEN WANG, CHEN CHEN, DING MA, LIU, Zhen-Jun, SHILIN YANG, JIANFENG ZHOU, XIAO XIAO, ZHANG, Xin A, EDIN, Matthew L
Format:	Article
Language:	eng
Subjects:	Animals Antineoplastic agents Biological and medical sciences Breast Neoplasms - pathology Cell Adhesion Cell Line, Tumor Cell Movement Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cytochrome P-450 Enzyme System - metabolism Cytochrome P-450 Enzyme System - physiology Fundamental and applied biological sciences. Psychology Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic General aspects Genetic Vectors Humans Lung Neoplasms - secondary Medical sciences Mice Mice, Inbred BALB C Molecular and cellular biology Neoplasm Metastasis Neoplasm Transplantation Oxygenases - metabolism Oxygenases - physiology Pharmacology. Drug treatments
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Cytochrome P450 (CYP) epoxygenases convert arachidonic acid to four regioisomeric epoxyeicosatrienoic acids (EET), which exert diverse biological activities in a variety of systems. We previously reported that the CYP2J2 epoxygenase is overexpressed in human cancer tissues and cancer cell lines and that EETs enhance tumor growth, increase carcinoma cell proliferation, and prevent apoptosis of cancer cells. Herein, we report that CYP epoxygenase overexpression or EET treatment promotes tumor metastasis independent of effects on tumor growth. In four different human cancer cell lines in vitro, overexpression of CYP2J2 or CYP102 F87V with an associated increase in EET production or addition of synthetic EETs significantly induced Transwell migration (4.5- to 5.5-fold), invasion of cells (3- to 3.5-fold), cell adhesion to fibronectin, and colony formation in soft agar. In contrast, the epoxygenase inhibitor 17-ODYA or infection with the antisense recombinant adeno-associated viral vector (rAAV)-CYP2J2 vector inhibited cell migration, invasion, and adhesion with an associated reduction in EET production. CYP overexpression also enhanced metastatic potential in vivo in that rAAV-CYP2J2-infected MDA-MB-231 human breast carcinoma cells showed 60% more lung metastases in athymic BALB/c mice and enhanced angiogenesis in and around primary tumors compared with control cells. Lung metastasis was abolished by infection with the antisense rAAV-CYP2J2 vector. CYP epoxygenase overexpression or EET treatment up-regulated the prometastatic matrix metalloproteinases and CD44 and down-regulated the antimetastatic genes CD82 and nm-23. Together, these data suggest that CYP epoxygenase inhibition may represent a novel approach to prevent metastasis of human cancers.
ISSN:	0008-5472 1538-7445