Arachidonate 5 lipoxygenase expression in papillary thyroid carcinoma promotes invasion via MMP-9 induction

Arachidonate 5‐lipoxygenase (ALOX5) expression and activity has been implicated in tumor pathogenesis, yet its role in papillary thyroid carcinoma (PTC) has not been characterized. ALOX5 protein and mRNA were upregulated in PTC compared to matched, normal thyroid tissue, and ALOX5 expression correla...

Full description

Saved in:

Bibliographic Details
Published in:	Journal of cellular biochemistry Vol. 113; no. 6; pp. 1998 - 2008
Main Authors:	Kummer, Nicolas T., Nowicki, Theodore S., Azzi, Jean P., Reyes, Ismael, Iacob, Codrin, Xie, Suqing, Swati, Ismatun, Darzynkiewicz, Zbigniew, Gotlinger, Katherine H., Suslina, Nina, Schantz, Stimson, Tiwari, Raj K., Geliebter, Jan
Format:	Journal Article
Language:	English
Published:	Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-06-2012
Subjects:	5-HETE Adult Aged ARACHIDONATE 5-LIPOXYGENASE Arachidonate 5-Lipoxygenase - genetics Arachidonate 5-Lipoxygenase - metabolism Biomarkers, Tumor Carcinoma Carcinoma, Papillary Cell Cycle Cell Line, Tumor Cell Movement Cell Proliferation EXTRACELLULAR MATRIX Extracellular Matrix - metabolism Female Humans Hydroxyeicosatetraenoic Acids - metabolism Hydroxyeicosatetraenoic Acids - pharmacology Lipoxygenase Inhibitors - pharmacology Male Matrix Metalloproteinase 9 - metabolism Matrix Metalloproteinase Inhibitors MATRIX METALLOPROTEINASE-9 Middle Aged Neoplasm Invasiveness PAPILLARY THYROID CARCINOMA RNA, Messenger - genetics RNA, Messenger - metabolism Thyroid Cancer, Papillary Thyroid Neoplasms - metabolism Thyroid Neoplasms - pathology TUMOR INVASION Young Adult
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Arachidonate 5‐lipoxygenase (ALOX5) expression and activity has been implicated in tumor pathogenesis, yet its role in papillary thyroid carcinoma (PTC) has not been characterized. ALOX5 protein and mRNA were upregulated in PTC compared to matched, normal thyroid tissue, and ALOX5 expression correlated with invasive tumor histopathology. Evidence suggests that PTC invasion is mediated through the induction of matrix metalloproteinases (MMPs) that can degrade and remodel the extracellular matrix (ECM). A correlation between MMP‐9 and ALOX5 protein expression was established by immunohistochemical analysis of PTC and normal thyroid tissues using a tissue array. Transfection of ALOX5 into a PTC cell line (BCPAP) increased MMP‐9 secretion and cell invasion across an ECM barrier. The ALOX5 product, 5(S)‐hydroxyeicosatetraenoic acid also increased MMP‐9 protein expression by BCPAP in a dose‐dependent manner. Inhibitors of MMP‐9 and ALOX5 reversed ALOX5‐enhanced invasion. Here we describe a new role for ALOX5 as a mediator of invasion via MMP‐9 induction; this ALOX5/MMP9 pathway represents a new avenue in the search for functional biomarkers and/or potential therapeutic targets for aggressive PTC. J. Cell. Biochem. 113: 1998–2008, 2012. © 2012 Wiley Periodicals, Inc.
Bibliography:	Department of Otolaryngology, New York Medical College, Valhalla, NY istex:4EA9BFF6C4BF540F037D476F7243C52D8F8D29B7 ArticleID:JCB24069 ark:/67375/WNG-BLM3J3XK-3 National Cancer Institute - No. 1R01CA131946-01A2 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0730-2312 1097-4644
DOI:	10.1002/jcb.24069