Glycoprotein-130 Expression Is Associated with Aggressive Bladder Cancer and Is a Potential Therapeutic Target

Abstract

Predicting bladder cancer progression is important in selecting the optimal treatment for bladder cancer. Because current diagnostic factors regarding progression are lacking, new factors are needed to further stratify the curative potential of bladder cancer. Glycoprotein-130 (GP130), a transmembrane protein, is central to a number of signal transduction pathways involved in tumor aggressiveness, making it an attractive target. We hypothesize that if GP130 is found in an aggressive population of bladder tumors, then blocking GP130 expression may inhibit bladder cancer growth. Herein, we quantitatively show, using 11 patient samples and four bladder cancer cell lines, that GP130 is expressed in the aggressive human bladder tumors and in high-grade bladder cancer cell lines. Moreover, GP130 is significantly correlated with tumor grade, node category, tumor category, and patient outcome. We demonstrated a tumor-specific GP130 effect by blocking GP130 expression in bladder tumor cells, which resulted in decreased cell viability and reduced cell migration. Furthermore, we reduced tumor volume by approximately 70% compared with controls by downregulating GP130 expression using chitosan-functionalized nanoparticles encapsulating GP130 siRNA in an in vivo bladder cancer xenograft mouse model. Our results indicate that GP130 expression is linked to the aggressiveness of bladder tumors, and blocking GP130 has therapeutic potential in controlling tumor growth.

Thymopentin alleviates premature ovarian failure in mice by activating YY2/Lin28A and inhibiting the expression of let‐7 family microRNAs

“…Cytotoxicity analysis and use of xenograft tumour models showed that DTX/TPGS‐loaded porous PLGA nanoparticles had a more obvious anti‐tumour effect and that the inhibitory effect on HeLa cells was greater than that of PLGA nanoparticles without TPGS, the former inhibited multidrug resistance and enhanced the overall anti‐tumour effect 34 . Martin et al 21 used chitosan‐modified PLGA nanoparticles to target a silencing siRNA oligoRNA (siGP130@PLGA) of GP130 and injected it into a mouse model of bladder cancer xenotransplantation; these authors achieved the goal of over‐expression of siRNA in vivo, thus significantly downregulating endogenous GP130 21 . Their experimental results suggested that siGP130@PLGA injection reduced tumour volume by approximately 70% compared with the control group 21 .…”

“…Our methods were performed according to previous reports 13,21‐23 . Briefly, YY2‐siRNA (siYY2) and random control (siMock) oligoRNAs were synthesized by GenePharma (GenePharma).…”

MicroRNA‐146b‐5p overexpression attenuates premature ovarian failure in mice by inhibiting the Dab2ip/Ask1/p38‐Mapk pathway and γH2A.X phosphorylation

“…However, the ability of PLGA to deliver miRs into cells or organs has not been reported. Based on the findings of Martin et al, 20 this study linked miR‐146 to chitosan‐functionalized PLGA nanoparticles to target p38‐Mapk14 in vitro and in vivo. PLGA could successfully deliver miR‐146 into OGCs in vitro and in vivo.…”

“…Here, miR‐146 specifically refers to miR‐146b‐5p. The miR‐146b‐5p (miR‐146) and miR‐mut oligo RNAs were synthesized by Genepharma as reported previously 20‐22 . PLGA (MedChemExpress) was dissolved in methylene chloride overnight.…”

Resveratrol, curcumin, paclitaxel and miRNAs mediated regulation of PI3K/Akt/mTOR pathway: go four better to treat bladder cancer

“…In an in vivo experiment, its high expression is reported to have a direct association with elevated phosphorylation of mAKT and mTOR, implying it as an obvious cause for rapid tumor growth and aggressiveness. Knocking down of GP130 via siRNA containing nano-particles caused a decrease in cell viability, tumor growth and migration in T24 and UM-UC-3 BC cell lines which suggested that gp130 might be a therapeutic target against tumor growth [ 45 ].…”