Impact of Sulfatase‐2 on cancer progression and prognosis in patients with renal cell carcinoma

Autor: Tomohiko Yanagida, Masao Kataoka, Yoshiyuki Kojima, Toshiki Oguro, Shin Kumagai, Ken Aikawa, Kei Ishibashi, Yuichirou Kiko
Rok vydání: 2016
Předmět:
Male
Vascular Endothelial Growth Factor A
0301 basic medicine
Cancer Research
Pathology
Cell
Cancer progression
Fibroblast growth factor
0302 clinical medicine
Cell
Molecular
and Stem Cell Biology
Renal cell carcinoma
Sulfatase‐2
Aged
80 and over
Wnt signaling pathway
General Medicine
Middle Aged
Prognosis
Kidney Neoplasms
Gene Expression Regulation
Neoplastic
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Disease Progression
Original Article
Female
Fibroblast Growth Factor 2
Sulfatases
Sulfotransferases
Signal Transduction
Adult
renal cell carcinoma
medicine.medical_specialty
Cell Survival
Biology
03 medical and health sciences
Cell Line
Tumor
medicine
Humans
Neoplasm Invasiveness
RNA
Messenger
Viability assay
Carcinoma
Renal Cell
Aged
heparan sulfate proteoglycan binding growth factor
Cancer
Original Articles
medicine.disease
Wnt Proteins
030104 developmental biology
Cell culture
Cancer research
Immunostaining
Zdroj: Cancer Science
ISSN: 1349-7006
1347-9032
Popis: Heparan sulfate-specific endosulfatase-2, SULF-2, can modulate the signaling of HSPG-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 (RCCs) 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 RCCs 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 RCCs and low SULF-2 RCCs 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. RCCs 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. This article is protected by copyright. All rights reserved.
Databáze: OpenAIRE
Externí odkaz: