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Updated: May 24, 2026
10:37
Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
FGFR2 isoforms support epithelial-stromal interactions in thyroid cancer progression.
Miao Guo1, Wei Liu, Stefano Serra
1The Ontario Cancer Institute, Department of Medicine, University Health Network, Toronto, Ontario, Canada.
Cancer Research
|February 21, 2012
Summary
Fibroblast growth factor (FGF) receptor variants FGFR2-IIIb and FGFR2-IIIc show tumor-suppressive effects in thyroid cancer cells but promote fibroblast growth, highlighting context-dependent functions.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Fibroblast growth factor (FGF) receptor (FGFR) expression is frequently dysregulated in human thyroid cancer.
- Alternate splicing of FGFR2 generates distinct isoforms, FGFR2-IIIb and FGFR2-IIIc, with varying extracellular structures.
Purpose of the Study:
- To investigate the functional roles of FGFR2-IIIb and FGFR2-IIIc isoforms in modulating thyroid cancer cell behavior.
- To understand the impact of these FGFR isoforms on tumor growth, invasion, and metastasis in vivo and in vitro.
- To explore the influence of cellular context on the growth-promoting or suppressing activities of FGFR isoforms.
Main Methods:
- Enforced expression of FGFR2-IIIb or FGFR2-IIIc in thyroid epithelial cancer cells.
- Assessment of gene expression changes (fibronectin, MAGE-A3, MMP9, p21) and Rb dephosphorylation.
- In vitro invasion assays and in vivo tumor growth and metastasis studies using xenograft models.
- Co-implantation experiments with epithelial and fibroblast cells expressing specific FGFR isoforms.
Main Results:
- Expression of FGFR2-IIIb or FGFR2-IIIc in thyroid cancer cells reduced fibronectin, MAGE-A3, and MMP9, while increasing p21 and Rb dephosphorylation.
- Both isoforms exhibited tumor-suppressive properties, diminishing invasion in vitro and reducing tumor growth and metastasis in vivo.
- In contrast, these isoforms stimulated fibroblast cell growth.
- Co-expression of FGFR2-IIIb in epithelial cells and FGFR2-IIIc in fibroblasts enhanced tumor progression, indicating context-dependent effects.
Conclusions:
- Cellular context is crucial in determining the growth-modulating properties of FGF receptor isoforms.
- Alternative splicing of FGFR2 generates heteroisoforms with distinct epithelial-stromal effects critical for FGF-mediated growth promotion in thyroid cancer.
- These findings underscore the complex roles of FGFR isoforms in thyroid cancer progression and suggest potential therapeutic targets.
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