Identification of a fibroblast growth factor receptor 1 splice variant that inhibits pancreatic cancer cell growth
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Updated: Jul 16, 2026
A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
Published on: December 22, 2020
Zhanbing Liu1, Nicola Neiss, Shaoxia Zhou
1Department of General, Visceral and Transplantation Surgery, University of Ulm, Ulm, Germany.
Abstract:
Fibroblast growth factor receptors (FGFR) play important roles in many biological processes. Nothing is presently known about possible roles of the human FGFR1-IIIb mRNA splice variant. In this study, we characterized for the first time the effects of FGFR1-IIIb expression on the transformed phenotype of human pancreatic cancer cells. The full-length FGFR1-IIIb cDNA was generated and stably expressed in PANC-1 and MIA PaCa-2 pancreatic cancer and TAKA-1 pancreatic ductal cells. FGFR1-IIIb-expressing cells synthesized a glycosylated 110-kDa protein enhancing tyrosine phosphorylation of FGFR substrate-2 on FGF-1 stimulation. The basal anchorage-dependent and anchorage-independent cell growth was significantly inhibited. These effects were associated with a marked reduction of p44/42 mitogen-activated protein kinase (MAPK) phosphorylation in combination with enhanced activity of p38 MAPK and c-Jun NH(2)-terminal kinase. FGFR1-IIIb expression inhibited single-cell movement and in vitro invasion as determined by time-lapse microscopy and Boyden chamber assay as well as in vivo tumor formation and growth in nude mice. Microscopic analysis of the xenograft tumors revealed a reduced Ki-67 labeling and a lower amount of tumor necrosis in FGFR1-IIIb-expressing tumors. Our results show that FGFR1-IIIb is a functional FGFR that inhibits the transformed phenotype of human pancreatic cancer cells.
Insights
Fibroblast growth factor receptor 1 (FGFR1)-IIIb inhibits pancreatic cancer growth. This study shows FGFR1-IIIb suppresses tumor formation, invasion, and cell growth in human pancreatic cancer cells.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Fibroblast growth factor receptors (FGFRs) are crucial in biological processes.
- The role of the human FGFR1-IIIb mRNA splice variant in cancer is unknown.
Purpose of the Study:
- To investigate the effects of FGFR1-IIIb expression on the transformed phenotype of human pancreatic cancer cells.
- To characterize FGFR1-IIIb as a functional receptor inhibiting cancer cell growth.
Main Methods:
- Stable expression of full-length FGFR1-IIIb cDNA in human pancreatic cancer cell lines (PANC-1, MIA PaCa-2, TAKA-1).
- Assessed protein synthesis, tyrosine phosphorylation, cell growth (anchorage-dependent and independent), MAPK signaling pathways, cell movement, invasion, and tumor formation in vivo.
- Analyzed xenograft tumors for Ki-67 labeling and necrosis.
Main Results:
- FGFR1-IIIb expression resulted in a 110-kDa glycosylated protein, enhancing FGFR substrate-2 phosphorylation upon FGF-1 stimulation.
- Significant inhibition of anchorage-dependent and independent cell growth.
- Reduced p44/42 MAPK phosphorylation, increased p38 MAPK and c-Jun NH(2)-terminal kinase activity.
- Inhibited cell movement, in vitro invasion, and in vivo tumor formation and growth.
- Reduced Ki-67 labeling and tumor necrosis in xenografts.
Conclusions:
- FGFR1-IIIb functions as a tumor suppressor in human pancreatic cancer.
- FGFR1-IIIb expression effectively inhibits the transformed phenotype of pancreatic cancer cells.
