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00085472can132513-sup-118521_2_supp_2510517_n6x85d.ppt (334.5 kB)

Supplemental Figure 2 from MYCN-Dependent Expression of Sulfatase-2 Regulates Neuroblastoma Cell Survival

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posted on 2023-03-30, 22:25 authored by Valeria Solari, Lucia Borriello, Gianluca Turcatel, Hiroyuki Shimada, Richard Sposto, G. Esteban Fernandez, Shahab Asgharzadeh, Edwin A. Yates, Jeremy E. Turnbull, Yves A. DeClerck

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ARTICLE ABSTRACT

Heparan sulfate proteoglycans (HSPG) play a critical role in the interaction of tumor cells and their microenvironment. HSPG activity is dictated by sulfation patterns controlled by sulfotransferases, which add sulfate groups, and sulfatases (Sulf), which remove 6-O-sulfates. Here, we report altered expression of these enzymes in human neuroblastoma cells with higher levels of Sulf-2 expression, a specific feature of MYCN-amplified cells (MYCN-A cells) that represent a particularly aggressive subclass. Sulf-2 overexpression in neuroblastoma cells lacking MYCN amplification (MYCN-NA cells) increased their in vitro survival. Mechanistic investigations revealed evidence of a link between Sulf-2 expression and MYCN pathogenicity in vitro and in vivo. Analysis of Sulf-2 protein expression in 65 human neuroblastoma tumors demonstrated a higher level of Sulf-2 expression in MYCN-A tumors than in MYCN-NA tumors. In two different patient cohorts, we confirmed the association in expression patterns of Sulf-2 and MYCN and determined that Sulf-2 overexpression predicted poor outcomes in a nonindependent manner with MYCN. Our findings define Sulf-2 as a novel positive regulator of neuroblastoma pathogenicity that contributes to MYCN oncogenicity. Cancer Res; 74(21); 5999–6009. ©2014 AACR.

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