Inhibition of transforming growth factor alpha stimulation of human squamous cell carcinoma of the head and neck with anti-TGF-alpha antibodies and tyrphostin.

Solorzano CC, Jones SC, Pettitjean M, O'Daniel TG, Auffenberg T, Woost PG, Copeland EM, Moldawer LL, Schultz GS, MacKay SL
Ann Surg Oncol. 1997 4 (8): 670-84

PMID: 9416416 · DOI:10.1007/bf02303753

BACKGROUND - Transforming growth factor alpha (TGF-alpha) and its receptor (EGF-R) may regulate normal and malignant epithelial cell growth by an autocrine mechanism. We investigated the role of TGF-alpha in regulating head and neck SCC tumor growth.

METHODS - TGF-alpha and EGF-R levels were measured in 7 SCC cell lines and 14 SCC biopsies by RIA, Scatchard, and Western analysis. TGF-alpha autocrine stimulation of DNA synthesis in SCC cell lines was assessed by incubation with TGF-alpha neutralizing antibodies and tyrphostin AG 1478, a selective and potent inhibitor of EGF-R kinase.

RESULTS - All SCC cell lines synthesized TGF-alpha and expressed elevated EGF-R levels compared to normal keratinocytes. Twelve of the 14 SCC biopsies contained TGF-alpha protein and 8 had specific EGF-R. Exogenous TGF-alpha or EGF significantly increased DNA synthesis in 4 of 5 SCC cell lines. TGF-alpha neutralizing antibodies or tyrphostin AG 1478 reduced DNA synthesis in the two SCC cell lines (FaDu and SCC9) tested.

CONCLUSIONS - These results indicate that SCC cell lines and tumors usually synthesize TGF-alpha, have elevated levels of EGF-R, and are mitogenically stimulated by a TGF-alpha autocrine system. Selective inhibition of the TGF-alpha system by EGF-R kinase inhibitors or TGF-alpha neutralizing antibodies may be useful strategies for treating SCC that overexpress TGF-alpha and its receptor.

MeSH Terms (10)

Autocrine Communication Carcinoma, Squamous Cell DNA, Neoplasm ErbB Receptors Head and Neck Neoplasms Humans Protein-Tyrosine Kinases Regression Analysis Transforming Growth Factor alpha Tumor Cells, Cultured

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