SULFs in human neoplasia: implication as progression and prognosis factors. - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Journal of Translational Medicine Year : 2011

SULFs in human neoplasia: implication as progression and prognosis factors.


ABSTRACT: BACKGROUND: 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. METHODS: 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. RESULTS: We demonstrated that SULF2 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 SULF2 gene expression in skin cancer, colorectal carcinoma, testicular teratoma and liver cancer compared to their normal tissue counterpart. We found that SULF2 was significantly over-expressed in high grade uveal melanoma compared to low grade and in patients presenting colorectal carcinoma compared to benign colon adenoma. We observed that, in addition to previous observations, SULF1 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 SULF1 expression was associated with a poor prognosis in lung adenocarcinoma. Finally, SULF1 and SULF2 were simultaneously overexpressed in 6 cancer types: brain, breast, head and neck, renal, skin and testicular cancers. CONCLUSIONS: SULF1 and SULF2 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.


Fichier principal
Vignette du fichier
1479-5876-9-72.pdf (330.52 Ko) Télécharger le fichier
1479-5876-9-72.xml (174.96 Ko) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Format : Other

Dates and versions

inserm-00601153 , version 1 (16-06-2011)



Caroline Bret, Jérôme Moreaux, Jean-François Schved, Dirk Hose, Bernard Klein. SULFs in human neoplasia: implication as progression and prognosis factors.. Journal of Translational Medicine, 2011, 9 (1), pp.72. ⟨10.1186/1479-5876-9-72⟩. ⟨inserm-00601153⟩
112 View
178 Download



Gmail Facebook Twitter LinkedIn More