SULF2 overexpression positively regulates tumorigenicity of human prostate cancer cells

Autor(es)

Vicente, Carolina M. ^[1] ; Lima, Marcelo A. ^{[1, 2]} ; Nader, Helena B. ^[1] ; Toma, Leny ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, UNIFESP, Dept Bioquim, Disciplina Biol Mol, BR-04044020 Sao Paulo, SP - Brazil

^[2] Univ Liverpool, Dept Biochem, Inst Integrat Biol, Liverpool L69 3BX, Merseyside - England

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH; v. 34, MAR 14 2015.
• Citações Web of Science: 9

Resumo

Background: SULF2 is a 6-O-endosulfatase which removes 6-O sulfate residues from N-glucosamine present on heparan sulfate (HS). The sulfation pattern of HS influences signaling events mediated by heparan sulfate proteoglycans (HSPGs) located on cell surface, which are critical for the interactions with growth factors and their receptors. Alterations in SULF2 expression have been identified in the context of several cancer types but its function in cancer is still unclear where the precise molecular mechanism involved has not been fully deciphered. To further investigate SULF2 role in tumorigenesis, we overexpressed such gene in prostate cancer cell lines. Methods: The normal prostate epithelial cell line RWPE-1 and the prostate cancer cells DU-145, and PC3 were transfected with SULF2-expressing plasmid pcDNA3.1/Myc-His(-)-Hsulf-2. Transfected cells were then submitted to viability, migration and colony formation assays. Results: Transfection of DU-145 and PC3 prostate cancer cells with SULF2 resulted in increased viability, which did not occur with normal prostate cells. The effect was reverted by the knockdown of SULF2 using specific siRNAs. Furthermore, forced expression of SULF2 augmented cell migration and colony formation in both prostate cell lines. Detailed structural analysis of HS from cells overexpressing SULF2 showed a reduction of the trisulfated disaccharide UA(2S)-GlcNS(6S). There was an increase in epithelial-mesenchymal transition markers and an increase in WNT signaling pathway. Conclusions: These results indicate that SULF2 have a pro-tumorigenic effect in DU-145 and PC3 cancer cells, suggesting an important role of this enzyme in prostatic cancer metastasis. (AU)

• Processo FAPESP: 09/52430-3 - Microscopia laser aplicada na biologia celular e molecular
• Beneficiário: Helena Bonciani Nader
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/50024-0 - Papel dos proteoglicanos na biologia do cancer coloretal e de prostata humanos:um estudo in vitro do seu microambiente tumoral.
• Beneficiário: Leny Toma
• Modalidade de apoio: Auxílio à Pesquisa - Regular