A Enomoto

AH Merrill

Alfred H Merrill

AM Makhlouf

Amin Momin

AS Don

BN Marbois

C Gnewuch

C Riebeling

DS Cornett

E Astigarraga

EL Kean

Elaine Wang

FF Hsu

H Morichika

J Garcia

J Li

JF Harris

John F McDonald

K Shikata

KD Dahlquist

KE Burnum

KT Kiguchi

L DeEtte Walker

Lilya V Matyunina

M Cameron Sullards

M Kanehisa

MD Wang

MR Groseclose

N Hiraiwa

N Sakakibara

Nathan J Bowen

NC Hait

NJ Bowen

PE Schwartz

Rebecca Shaner

RH Kim

RL Shaner

S Hakomori

S Warrenfeltz

SA Schwartz

SN Jackson

T Hornemann

TM Robinson-Smith

Y Chen

Yanfeng Chen

Ying Liu

ZV Popovic

Molecular Cancer

English

PubMed

Abstract
          
            Background
            Sulfatides (ST) are a category of sulfated galactosylceramides (GalCer) that are elevated in many types of cancer including, possibly, ovarian cancer. Previous evidence for elevation of ST in ovarian cancer was based on a colorimetric reagent that does not provide structural details and can also react with other lipids. Therefore, this study utilized mass spectrometry for a structure-specific and quantitative analysis of the types, amounts, and tissue localization of ST in ovarian cancer, and combined these findings with analysis of mRNAs for the relevant enzymes of ST metabolism to explore possible mechanisms.
          
          
            Results
            Analysis of 12 ovarian tissues graded as histologically normal or having epithelial ovarian tumors by liquid chromatography electrospray ionization-tandem mass spectrometry (LC ESI-MS/MS) established that most tumor-bearing tissues have higher amounts of ST. Because ovarian cancer tissues are comprised of many different cell types, histological tissue slices were analyzed by matrix-assisted laser desorption ionization-tissue-imaging MS (MALDI-TIMS). The regions where ST were detected by MALDI-TIMS overlapped with the ovarian epithelial carcinoma as identified by H &amp; E staining and histological scoring. Furthermore, the structures for the most prevalent species observed via MALDI-TIMS (d18:1/C16:0-, d18:1/C24:1- and d18:1/C24:0-ST) were confirmed by MALDI-TIMS/MS, whereas, a neighboring ion(m/z 885.6) that was not tumor specific was identified as a phosphatidylinositol. Microarray analysis of mRNAs collected using laser capture microdissection revealed that expression of GalCer synthase and Gal3ST1 (3'-phosphoadenosine-5'-phosphosulfate:GalCer sulfotransferase) were approximately 11- and 3.5-fold higher, respectively, in the ovarian epithelial carcinoma cells versus normal ovarian stromal tissue, and they were 5- and 2.3-fold higher in comparison with normal surface ovarian epithelial cells, which is a likely explanation for the higher ST.
          
          
            Conclusions
            This study combined transcriptomic and lipidomic approaches to establish that sulfatides are elevated in ovarian cancer and should be evaluated further as factors that might be important in ovarian cancer biology and, possibly, as biomarkers.
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Elevation of sulfatides in ovarian cancer: An integrated transcriptomic and lipidomic analysis including tissue-imaging mass spectrometry

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