title: Impact of Sulfatase-2 on cancer progression and prognosis in patients with renal cell carcinoma.
abstract: Heparan sulfate-specific endosulfatase-2 (SULF-2) can modulate the signaling of heparan sulfate proteoglycan-binding proteins. The involvement of SULF-2 in cancer growth varies by cancer type. The roles of SULF-2 expression in the progression and prognosis of renal cell carcinomas (RCC) have not yet been fully clarified. In the present study, the expression levels of SULF-2 mRNA and protein in 49 clinical RCC samples were determined by RT-PCR and immunostaining. The existence of RCC with higher SULF-2 expression and lower SULF-2 expression compared to the adjacent normal kidney tissues was suggested. High SULF-2 expression was correlated with an early clinical stage and less invasive pathological factors. Low SULF-2 expression was correlated with an advanced stage and higher invasive factors. Three-year cancer-specific survival (CSS) for high SULF-2 RCC and low SULF-2 RCC were 100% and 71.4%, respectively (log-rank P = 0.0019), with a significantly shorter CSS observed in low SULF-2 RCC patients. The influence of SULF-2 expression level on Wnt/VEGF/FGF signaling, cell viability and invasive properties was examined in three RCC cell lines, Caki-2, ACHN and 786-O, using a SULF-2 suppression model involving siRNA or a SULF-2 overexpression model involving a plasmid vector. High SULF-2 expression enhanced Wnt signaling and Wnt-induced cell viability, but not cell invasion. In contrast, low levels of SULF-2 expression significantly enhanced both cell invasion and viability through the activation of VEGF/FGF pathways. RCC with lower SULF-2 expression might have a higher potential for cell invasion and proliferation, leading to a poorer prognosis via the activation of VEGF and/or FGF signaling.
authors: Department of Urology, Fukushima Medical University, Fukushima, Japan.
authors: Shin
authors: S
authors: Kumagai
authors: Department of Urology, Fukushima Medical University, Fukushima, Japan.
authors: Kei
authors: K
authors: Ishibashi
authors: Department of Urology, Fukushima Medical University, Fukushima, Japan.
authors: Masao
authors: M
authors: Kataoka
authors: Department of Urology, Fukushima Medical University, Fukushima, Japan.
authors: Toshiki
authors: T
authors: Oguro
authors: Department of Pathology, Fukushima Medical University, Fukushima, Japan.
authors: Yuichirou
authors: Y
authors: Kiko
authors: Department of Urology, Fukushima Medical University, Fukushima, Japan.
authors: Tomohiko
authors: T
authors: Yanagida
authors: Department of Urology, Fukushima Medical University, Fukushima, Japan.
authors: Ken
authors: K
authors: Aikawa
authors: Department of Urology, Fukushima Medical University, Fukushima, Japan.
authors: Yoshiyuki
authors: Y
authors: Kojima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D018450:Disease Progression; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D015398:Signal Transduction; D013429:Sulfatases; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051153:Wnt Proteins; D016222:Fibroblast Growth Factor 2; D015238:Sulfotransferases; C470792:SULF2 protein, human; D013429:Sulfatases
keywords: Cancer progression; Sulfatase-2; heparan sulfate proteoglycan binding growth factor; prognosis; renal cell carcinoma