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Updated: Jun 12, 2026
3-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer
Published on: September 13, 2018
Gli2 expression and human bladder transitional carcinoma cell invasiveness
Clay W Mechlin1, Matthew J Tanner, Mengqian Chen
1Division of Urology, Albany Medical College, Albany, New York, USA. mianb@mail.amc.edu
Purpose:
Hedgehog signaling regulates Gli transcription factors. Aberrant hedgehog signaling can be oncogenic and drugs that block hedgehog are being tested as anticancer agents. We considered whether hedgehog/Gli signaling may be involved in human bladder transitional cell carcinoma proliferative or invasive behavior.
Materials And Methods:
We stratified the human bladder transitional cell carcinoma lines RT4 (ATCC), 253JP, 253BV, UMUC6 and UMUC3 for relative growth rate by cell counting and for in vitro invasiveness by Matrigel invasion assay. Cells were tested for growth inhibition by the hedgehog blocking drug cyclopamine or the inactive mimic tomatidine. Cell RNA was characterized for hedgehog signaling component expression, including ligands, receptors and signaling mediators, by quantitative reverse transcriptase-polymerase chain reaction. Gli2 expression or activity was modified by Gli2 expression lentiviruses or the Gli inhibitor GANT61. We measured effects on proliferation and invasiveness.
Results:
Cell growth rates and invasiveness were stratified into an equivalent order (RT4 <243JP <253BV
Conclusions:
Weak growth suppression by cyclopamine suggests that hedgehog signaling is not involved in bladder cancer cell proliferation but Gli2 expression strongly correlated with invasive behavior. Increased Gli2 expression increased low Gli2 cell invasiveness while Gli inhibition by GANT61 decreased high Gli2 cell invasiveness. Results suggest that Gli2 expression by noncanonical signaling contributes to bladder cancer cell invasiveness.
Insights
Gli2 expression, not hedgehog signaling, drives bladder cancer cell invasiveness. This study reveals Gli2
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Hedgehog signaling pathway regulates Gli transcription factors.
- Aberrant hedgehog signaling is implicated in oncogenesis.
- Targeting hedgehog signaling is a strategy for anticancer drug development.
Purpose of the Study:
- To investigate the role of hedgehog/Gli signaling in human bladder transitional cell carcinoma (TCC).
- To determine the involvement of hedgehog/Gli signaling in the proliferative and invasive behaviors of bladder TCC cells.
Main Methods:
- Stratified human bladder TCC cell lines based on growth rate and invasiveness.
- Assessed growth inhibition using hedgehog pathway inhibitors (cyclopamine) and inactive controls (tomatidine).
- Quantified expression of hedgehog signaling components via RT-PCR.
- Manipulated Gli2 expression and activity to evaluate effects on proliferation and invasiveness.
Main Results:
- Cell invasiveness and growth rates were stratified across tested bladder TCC lines.
- Weak growth inhibition observed with tomatidine and cyclopamine across all cell lines.
- Gli2 expression levels correlated with cell invasiveness, unlike other hedgehog pathway components.
- Modulating Gli2 expression or activity significantly impacted cell invasiveness.
Conclusions:
- Hedgehog signaling does not appear to drive bladder cancer cell proliferation.
- Gli2 expression is strongly associated with bladder cancer cell invasive behavior.
- Gli2, potentially through noncanonical signaling, contributes to bladder cancer invasiveness.
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