title: Arachidonate 5 lipoxygenase expression in papillary thyroid carcinoma promotes invasion via MMP-9 induction.
abstract: 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.
authors.affiliation: Department of Microbiology & Immunology, New York Medical College, Valhalla, New York 10595, USA.
authors.forename: Nicolas T
authors.initials: NT
authors.lastname: Kummer
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Nowicki
authors.forename: Jean P
authors.initials: JP
authors.lastname: Azzi
authors.forename: Ismael
authors.initials: I
authors.lastname: Reyes
authors.forename: Codrin
authors.initials: C
authors.lastname: Iacob
authors.forename: Suqing
authors.initials: S
authors.lastname: Xie
authors.forename: Ismatun
authors.initials: I
authors.lastname: Swati
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Darzynkiewicz
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Gotlinger
authors.forename: Nina
authors.initials: N
authors.lastname: Suslina
authors.forename: Stimson
authors.initials: S
authors.lastname: Schantz
authors.forename: Raj K
authors.initials: RK
authors.lastname: Tiwari
authors.forename: Jan
authors.initials: J
authors.lastname: Geliebter
mesh_terms: D000328:Adult; D000368:Aged; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor; D002277:Carcinoma; D002291:Carcinoma, Papillary; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism* / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D006893:Hydroxyeicosatetraenoic Acids; D016859:Lipoxygenase Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D001094:Arachidonate 5-Lipoxygenase; D020780:Matrix Metalloproteinase 9