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

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Abstract

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

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

Results: All SCC cell lines synthesized TGF-α and expressed elevated EGF-R levels compared to normal keratinocytes. Twelve of the 14 SCC biopsies contained TGF-α protein and 8 had specific EGF-R. Exogenous TGF-α or EGF significantly increased DNA synthesis in 4 of 5 SCC cell lines. TGF-α 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-α, have elevated levels of EGF-R, and are mitogenically stimulated by a TGF-α autocrine system. Selective inhibition of the TGF-α system by EGF-R kinase inhibitors or TGF-α neutralizing antibodies may be useful strategies for treating SCC that overexpress TGF-α and its receptor.

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Authors and Affiliations

  1. the Department of Biochemistry, Division of Otolaryngology, University of Louisville, Louisville, Kentucky

    Philip G. Woost PhD

  2. the Department of Anatomical Sciences and Neurobiology, Division of Otolaryngology, University of Louisville, Louisville, Kentucky

    Shawn C. Jones MD

  3. the Department of Surgery, Division of Otolaryngology, University of Louisville, Louisville, Kentucky

    Shawn C. Jones MD & Thomas G. O'Daniel MD

  4. Department of Obstetrics and Gynecology, University of Florida, Gainesville, Florida, USA

    Gregory S. Schultz PhD

  5. Dept. of Surgery, Box 100286, J. H. Miller Health Center, University of Florida, 32610, Gainesville, FL, USA

    Carmen C. Solorzano MD, Troy Auffenberg BS, Edward M. Copeland III MD, Lyle L. Moldawer PhD &  Sally L. D. MacKay PhD

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  1. Carmen C. Solorzano MD
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Solorzano, C.C., Jones, S.C., Pettitjean, M. et al. Inhibition of transforming growth factor alpha stimulation of human squamous cell carcinoma of the head and neck with anti-TGF-α antibodies and tyrphostin. Annals of Surgical Oncology 4, 670–684 (1997). https://doi.org/10.1007/BF02303753

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