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Elevation of sulfatides in ovarian cancer: an integrated transcriptomic and lipidomic analysis including tissue-imaging mass spectrometry.

Liu Y, Chen Y, Momin A, Shaner R, Wang E, Bowen NJ, Matyunina LV, Walker LD, McDonald JF, Sullards MC, Merrill AH - Mol. Cancer (2010)

Bottom Line: The regions where ST were detected by MALDI-TIMS overlapped with the ovarian epithelial carcinoma as identified by H & 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Biology and the Petit Institute for Bioscience and Bioengineering, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, Georgia 30332-0363, USA.

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 & 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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Related in: MedlinePlus

Visualization of phosphatidylinositol and ST in a thin section of normal ovarian tissue using MALDI TIMS. Adjacent thin sections of normal ovarian tissue was prepared as described in the text for H & E staining (A) and pseudo-color ion images for phosphatidylinositol (B) as a positive control (m/z 885.6 at the instrument calibration used for this image) and ST (at m/z 778.6, C; m/z 888.6, D; and m/z 890.6, E) using the shown heat map scale. The ovarian tissue in (A) has been manually traced with dashed lines, which have been superimposed on panels B-E to aid in comparison.
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Figure 8: Visualization of phosphatidylinositol and ST in a thin section of normal ovarian tissue using MALDI TIMS. Adjacent thin sections of normal ovarian tissue was prepared as described in the text for H & E staining (A) and pseudo-color ion images for phosphatidylinositol (B) as a positive control (m/z 885.6 at the instrument calibration used for this image) and ST (at m/z 778.6, C; m/z 888.6, D; and m/z 890.6, E) using the shown heat map scale. The ovarian tissue in (A) has been manually traced with dashed lines, which have been superimposed on panels B-E to aid in comparison.

Mentions: MALDI TIMS was also used to analyze a thin section from normal ovarian tissue. The image is shown in Figure 8, illustrating that the major ST (m/z 778.6, 888.6 and 890.6) were not detectable, whereas PI (m/z 885.6) was detectable and served as a positive control (Figure 8B).


Elevation of sulfatides in ovarian cancer: an integrated transcriptomic and lipidomic analysis including tissue-imaging mass spectrometry.

Liu Y, Chen Y, Momin A, Shaner R, Wang E, Bowen NJ, Matyunina LV, Walker LD, McDonald JF, Sullards MC, Merrill AH - Mol. Cancer (2010)

Visualization of phosphatidylinositol and ST in a thin section of normal ovarian tissue using MALDI TIMS. Adjacent thin sections of normal ovarian tissue was prepared as described in the text for H & E staining (A) and pseudo-color ion images for phosphatidylinositol (B) as a positive control (m/z 885.6 at the instrument calibration used for this image) and ST (at m/z 778.6, C; m/z 888.6, D; and m/z 890.6, E) using the shown heat map scale. The ovarian tissue in (A) has been manually traced with dashed lines, which have been superimposed on panels B-E to aid in comparison.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2913985&req=5

Figure 8: Visualization of phosphatidylinositol and ST in a thin section of normal ovarian tissue using MALDI TIMS. Adjacent thin sections of normal ovarian tissue was prepared as described in the text for H & E staining (A) and pseudo-color ion images for phosphatidylinositol (B) as a positive control (m/z 885.6 at the instrument calibration used for this image) and ST (at m/z 778.6, C; m/z 888.6, D; and m/z 890.6, E) using the shown heat map scale. The ovarian tissue in (A) has been manually traced with dashed lines, which have been superimposed on panels B-E to aid in comparison.
Mentions: MALDI TIMS was also used to analyze a thin section from normal ovarian tissue. The image is shown in Figure 8, illustrating that the major ST (m/z 778.6, 888.6 and 890.6) were not detectable, whereas PI (m/z 885.6) was detectable and served as a positive control (Figure 8B).

Bottom Line: The regions where ST were detected by MALDI-TIMS overlapped with the ovarian epithelial carcinoma as identified by H & 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Biology and the Petit Institute for Bioscience and Bioengineering, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, Georgia 30332-0363, USA.

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 & 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.

Show MeSH
Related in: MedlinePlus