Anti- or pro-proliferation – Conditional options for TGF-α and cetuximab in head and neck squamous cell carcinoma. Issue 1 (January 2015)

• Record Type: Journal Article
• Authors: Ekblad, Lars; Welinder, Charlotte; Kjellén, Elisabeth; Brun, Eva; Wennerberg, Johan
• Is Part Of: Oral oncology. Volume 51:Issue 1(2015:Jan.)
• Page Start: 46
• Page End: 52
• Publication Date: 2015-01
• Subjects: Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2014.08.019
• Languages: English
• ISSNs: 1368-8375

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab015"> <title id="st085">Summary</title> <sec> <title id="st090">Objectives</title> <p id="sp0060">Cetuximab is an epidermal growth factor receptor (EGFR)-targeting drug that has shown effects in head and neck squamous cell carcinoma (HNSCC). The effects are, however, small and have mainly been proven in a subset of patients, and the cost-effectiveness has been questioned. For this reason, we need to know more about the basic mechanisms controlling the effect of EGFR signalling on tumour growth.</p> </sec> <sec> <title id="st095">Materials and methods</title> <p id="sp0065">We investigated the effect of the EGFR ligand transforming growth factor alpha (TGF-α) and cetuximab, alone and in combination, on HNSCC cell lines, measuring proliferation and the activity of intracellular signalling pathways.</p> </sec> <sec> <title id="st100">Results</title> <p id="sp0070">In line with previous reports we found the majority of the cell lines to be growth-inhibited by TGF-α. Surprisingly, two of the cell lines, which were more thoroughly investigated, were either growth-inhibited or stimulated by both cetuximab and TGF-α, depending on the presence or absence of the other substance. We also present data indicating the existence of two different receptor activities emanating from the EGFR protein.</p> </sec> <sec> <title id="st105">Conclusion</title> <p id="sp0075">We therefore show that TGF-α can have both growth-stimulating and growth-inhibiting effects in the same cell line and that EGFR-targeting drugs can be similarly double-edged. The implication for such drugs is that the micro-environment within a tumour, and possibly within portions of a tumour, may influence the growth-inhibiting effect of the drug. There may also be important implications for our understanding of EGFR signalling and its influence on growth and development.</p> </sec> </abstract>