SULFs in human neoplasia: implication as progression and prognosis factors

<p>Abstract</p> <p>Background</p> <p>The sulfation pattern of heparan sulfate chains influences signaling events mediated by heparan sulfate proteoglycans located on cell surface. SULF1 and SULF2 are two endosulfatases able to cleave specific 6-O sulfate groups within t...

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Main Authors: Schved Jean-François, Moreaux Jérôme, Bret Caroline, Hose Dirk, Klein Bernard
Format: Article
Language:English
Published: BMC 2011-05-01
Series:Journal of Translational Medicine
Online Access:http://www.translational-medicine.com/content/9/1/72
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author Schved Jean-François
Moreaux Jérôme
Bret Caroline
Hose Dirk
Klein Bernard
author_facet Schved Jean-François
Moreaux Jérôme
Bret Caroline
Hose Dirk
Klein Bernard
author_sort Schved Jean-François
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>The sulfation pattern of heparan sulfate chains influences signaling events mediated by heparan sulfate proteoglycans located on cell surface. SULF1 and SULF2 are two endosulfatases able to cleave specific 6-O sulfate groups within the heparan chains. Their action can modulate signaling processes, many of which with key relevance for cancer development and expansion. SULF1 has been associated with tumor suppressor effects in various models of cancer, whereas SULF2 dysregulation was in relation with protumorigenic actions. However, other observations argue for contradictory effects of these sulfatases in cancer, suggesting the complexity of their action in the tumor microenvironment.</p> <p>Methods</p> <p>We compared the expression of the genes encoding SULF1, SULF2 and heparan sulfate proteoglycans in a large panel of cancer samples to their normal tissue counterparts using publicly available gene expression data, including the data obtained from two cohorts of newly-diagnosed multiple myeloma patients, the Oncomine Cancer Microarray database, the Amazonia data base and the ITTACA database. We also analysed prognosis data in relation with these databases.</p> <p>Results</p> <p>We demonstrated that <it>SULF2 </it>expression in primary multiple myeloma cells was associated with a poor prognosis in two independent large cohorts of patients. It remained an independent predictor when considered together with conventional multiple myeloma prognosis factors. Besides, we observed an over-representation of <it>SULF2 </it>gene expression in skin cancer, colorectal carcinoma, testicular teratoma and liver cancer compared to their normal tissue counterpart. We found that <it>SULF2 </it>was significantly over-expressed in high grade uveal melanoma compared to low grade and in patients presenting colorectal carcinoma compared to benign colon adenoma.</p> <p>We observed that, in addition to previous observations, <it>SULF1 </it>gene expression was increased in T prolymphocytic leukemia, acute myeloid leukemia and in renal carcinoma compared to corresponding normal tissues. Furthermore, we found that high <it>SULF1 </it>expression was associated with a poor prognosis in lung adenocarcinoma.</p> <p>Finally, <it>SULF1 </it>and <it>SULF2 </it>were simultaneously overexpressed in 6 cancer types: brain, breast, head and neck, renal, skin and testicular cancers.</p> <p>Conclusions</p> <p><it>SULF1 </it>and <it>SULF2 </it>are overexpressed in various human cancer types and can be associated to progression and prognosis. Targeting SULF1 and/or SULF2 could be interesting strategies to develop novel cancer therapies.</p>
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spelling doaj.art-56bdca6ac31e4d3081d98f4eb26bc5e52022-12-22T01:21:55ZengBMCJournal of Translational Medicine1479-58762011-05-01917210.1186/1479-5876-9-72SULFs in human neoplasia: implication as progression and prognosis factorsSchved Jean-FrançoisMoreaux JérômeBret CarolineHose DirkKlein Bernard<p>Abstract</p> <p>Background</p> <p>The sulfation pattern of heparan sulfate chains influences signaling events mediated by heparan sulfate proteoglycans located on cell surface. SULF1 and SULF2 are two endosulfatases able to cleave specific 6-O sulfate groups within the heparan chains. Their action can modulate signaling processes, many of which with key relevance for cancer development and expansion. SULF1 has been associated with tumor suppressor effects in various models of cancer, whereas SULF2 dysregulation was in relation with protumorigenic actions. However, other observations argue for contradictory effects of these sulfatases in cancer, suggesting the complexity of their action in the tumor microenvironment.</p> <p>Methods</p> <p>We compared the expression of the genes encoding SULF1, SULF2 and heparan sulfate proteoglycans in a large panel of cancer samples to their normal tissue counterparts using publicly available gene expression data, including the data obtained from two cohorts of newly-diagnosed multiple myeloma patients, the Oncomine Cancer Microarray database, the Amazonia data base and the ITTACA database. We also analysed prognosis data in relation with these databases.</p> <p>Results</p> <p>We demonstrated that <it>SULF2 </it>expression in primary multiple myeloma cells was associated with a poor prognosis in two independent large cohorts of patients. It remained an independent predictor when considered together with conventional multiple myeloma prognosis factors. Besides, we observed an over-representation of <it>SULF2 </it>gene expression in skin cancer, colorectal carcinoma, testicular teratoma and liver cancer compared to their normal tissue counterpart. We found that <it>SULF2 </it>was significantly over-expressed in high grade uveal melanoma compared to low grade and in patients presenting colorectal carcinoma compared to benign colon adenoma.</p> <p>We observed that, in addition to previous observations, <it>SULF1 </it>gene expression was increased in T prolymphocytic leukemia, acute myeloid leukemia and in renal carcinoma compared to corresponding normal tissues. Furthermore, we found that high <it>SULF1 </it>expression was associated with a poor prognosis in lung adenocarcinoma.</p> <p>Finally, <it>SULF1 </it>and <it>SULF2 </it>were simultaneously overexpressed in 6 cancer types: brain, breast, head and neck, renal, skin and testicular cancers.</p> <p>Conclusions</p> <p><it>SULF1 </it>and <it>SULF2 </it>are overexpressed in various human cancer types and can be associated to progression and prognosis. Targeting SULF1 and/or SULF2 could be interesting strategies to develop novel cancer therapies.</p>http://www.translational-medicine.com/content/9/1/72
spellingShingle Schved Jean-François
Moreaux Jérôme
Bret Caroline
Hose Dirk
Klein Bernard
SULFs in human neoplasia: implication as progression and prognosis factors
Journal of Translational Medicine
title SULFs in human neoplasia: implication as progression and prognosis factors
title_full SULFs in human neoplasia: implication as progression and prognosis factors
title_fullStr SULFs in human neoplasia: implication as progression and prognosis factors
title_full_unstemmed SULFs in human neoplasia: implication as progression and prognosis factors
title_short SULFs in human neoplasia: implication as progression and prognosis factors
title_sort sulfs in human neoplasia implication as progression and prognosis factors
url http://www.translational-medicine.com/content/9/1/72
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AT bretcaroline sulfsinhumanneoplasiaimplicationasprogressionandprognosisfactors
AT hosedirk sulfsinhumanneoplasiaimplicationasprogressionandprognosisfactors
AT kleinbernard sulfsinhumanneoplasiaimplicationasprogressionandprognosisfactors