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Decreased expression of transforming growth factor beta receptors on head and neck squamous cell carcinoma tumor
R J Eisma1, J D Spiro, S E von Biberstein
1Division of Otolaryngology, University of Connecticut Health Center, School of Medicine, Farmington 06030-3105, USA.
Background:
Transforming growth factor beta (TGF-beta) has antiproliferative effects on normal and neoplastic cells that express specific TGF-beta receptors. We hypothesize that diminished expression of TGF-beta and/or its receptors may contribute to the uncontrolled proliferation of head and neck squamous cell carcinoma (HNSCCA) cancer cells.
Methods:
Using immunohistochemical techniques, we characterized the expression of TGF-beta isoforms and TGF-beta receptors, TGF-beta(RI) and TGF-beta(RII), in HNSCCA. Tumor production of TGF-beta was evaluated in culture supernatants from a cytokine-stimulated HNSCCA tumor line (HTB-43).
Results:
All control specimens displayed strong cell-associated staining of TGF-beta as well as both receptors. Forty-seven of 47 cancer specimens exhibited positive staining for TGF-beta in the tumor matrix. Forty of the 47 cancer specimens demonstrated no expression of TGF-beta(RI), and 43 of the 47 expressed no TGF-beta(RII). Only interleukin 1 alpha (IL-1 alpha) and IL-1 beta induced significant TGF-beta expression from the HTB-43 cells.
Conclusions:
Decreased expression of TGF-beta receptors may play a significant role in the pathogenesis of HNSCCA by allowing uncontrolled cell proliferation.
Insights
Diminished expression of transforming growth factor beta (TGF-beta) receptors is linked to uncontrolled head and neck squamous cell carcinoma (HNSCCA) proliferation. This suggests a key role for TGF-beta signaling in HNSCCA development.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Transforming growth factor beta (TGF-beta) normally inhibits cell proliferation.
- Head and neck squamous cell carcinoma (HNSCCA) cells exhibit uncontrolled growth.
- Reduced expression of TGF-beta or its receptors may underlie HNSCCA proliferation.
Purpose of the Study:
- To investigate the expression of TGF-beta isoforms and their receptors in HNSCCA.
- To determine the role of TGF-beta signaling in HNSCCA pathogenesis.
Main Methods:
- Immunohistochemical analysis of TGF-beta, TGF-beta receptor type I (TGF-beta(RI)), and TGF-beta receptor type II (TGF-beta(RII)) expression in HNSCCA specimens.
- Evaluation of TGF-beta production by a cytokine-stimulated HNSCCA cell line (HTB-43).
Main Results:
- Control tissues showed strong TGF-beta and receptor expression.
- HNSCCA tumor matrices consistently stained positive for TGF-beta.
- A significant majority of HNSCCA specimens lacked TGF-beta(RI) (40/47) and TGF-beta(RII) (43/47) expression.
- Interleukin-1 alpha and -1 beta significantly induced TGF-beta production in HNSCCA cells.
Conclusions:
- Downregulation of TGF-beta receptors is implicated in HNSCCA pathogenesis.
- Loss of TGF-beta receptor expression may facilitate uncontrolled HNSCCA cell proliferation.