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.