Fibroblast growth factor receptors are components of autocrine signaling networks in head and neck squamous cell carcinoma cells.

Abstract

PURPOSE:

We previously reported that a fibroblast growth factor (FGF) receptor (FGFR) signaling pathway drives growth of lung cancer cell lines of squamous and large cell histologies. Herein, we explored FGFR dependency in cell lines derived from the tobacco-related malignancy, head and neck squamous cell carcinoma (HNSCC).

EXPERIMENTAL DESIGN:

FGF and FGFR mRNA and protein expression was assessed in nine HNSCC cell lines. Dependence on secreted FGF2 for cell growth was tested with FP-1039, an FGFR1-Fc fusion protein. FGFR and epidermal growth factor receptor (EGFR) dependence was defined by sensitivity to multiple inhibitors selective for FGFRs or EGFR.

RESULTS:

FGF2 was expressed in eight of the nine HNSCC cell lines examined. Also, FGFR2 and FGFR3 were frequently expressed, whereas only two lines expressed FGFR1. FP-1039 inhibited growth of HNSCC cell lines expressing FGF2, identifying FGF2 as an autocrine growth factor. FGFR inhibitors selectively reduced in vitro growth and extracellular signal-regulated kinase signaling in three HNSCC cell lines, whereas three distinct lines exhibited responsiveness to both EGFR and FGFR inhibitors. Combinations of these drugs yielded additive growth inhibition. Finally, three cell lines were highly sensitive to EGFR tyrosine kinase inhibitors (TKI) with no contribution from FGFR pathways.

CONCLUSIONS:

FGFR signaling was dominant or codominant with EGFR in six HNSCC lines, whereas three lines exhibited little or no role for FGFRs and were highly EGFR dependent. Thus, the HNSCC cell lines can be divided into subsets defined by sensitivity to EGFR and FGFR-specific TKIs. FGFR inhibitors may represent novel therapeutics to deploy alone or in combination with EGFR inhibitors in HNSCC.

• Authors: Marianne E Marshall, Trista K Hinz, Scott A Kono, Katherine R Singleton, Brady Bichon, Kathryn E Ware, Lindsay Marek, Barbara A Frederick, David Raben, Lynn E Heasley
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 17 Issue 15 Pg. 5016-25 (Aug 01 2011) ISSN: 1557-3265 [Electronic] United States
• PMID: 21673064 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: ©2011 AACR.

Chemical References

• Receptors, Fibroblast Growth Factor
• Fibroblast Growth Factor 2
• ErbB Receptors
• Protein-Tyrosine Kinases

Topics

• Autocrine Communication
• Carcinoma, Squamous Cell (metabolism)
• Cell Line, Tumor
• ErbB Receptors (metabolism)
• Fibroblast Growth Factor 2 (metabolism)
• Head and Neck Neoplasms (metabolism)
• Humans
• Protein-Tyrosine Kinases (antagonists & inhibitors)
• Receptors, Fibroblast Growth Factor (metabolism)
• Signal Transduction
• Squamous Cell Carcinoma of Head and Neck