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

Abstract

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.

Comparison of Myofibroblasts Expression in Oral Squamous Cell Carcinoma, Verrucous Carcinoma, High Risk Epithelial Dysplasia, Low Risk Epithelial Dysplasia and Normal Oral Mucosa

“…This happens as a result of induction by a variety of cytokines from cancerous cells [1]. OSCC cells have been shown to secrete high amounts of cytokines and growth factors such as TGFb1, TGF-a, IGF-related factors, and interleukins [36][37][38][39]. TGF-b1, in particular, is responsible for the fibroblast to myofibroblast transdifferentiation in experimental models [40].…”

TACE cleavage of proamphiregulin regulates GPCR-induced proliferation and motility of cancer cells

“…Previous studies showed that basal EGFR and ERK1/2 activities as well as cell proliferation are significantly reduced by batimastat and AG1478 (Gschwind et al ., 2002; O‐Charoenrat et al ., 2002), arguing for the existence of autocrine EGFR activation loops that require metalloprotease activity for EGFR ligand shedding. Furthermore, anti‐TGF‐α neutralizing antibodies reduced proliferation of SCC‐9 and FaDu cells (Solorzano et al ., 1997), and TGF‐α antisense therapy recently has been shown to inhibit HNSCC tumour growth in nude mice (Endo et al ., 2000). Collectively, these studies demonstrate a critical role for TGF‐α in autocrine stimulation of the EGFR resulting in sustained proliferation of HNSCC cells, while our current data establish a function for AR in GPCR‐induced cellular responses.…”

TGF-α antisense gene therapy inhibits head and neck squamous cell carcinoma growth in vivo

“…TGF-␣ monoclonal antibody treatment has been shown to inhibit the growth of lung cancer cell lines, 38 chemically induced mouse intestine cancer cells, 39 and human colon cancer cell lines in vitro. 40 DNA synthesis is reportedly decreased in both HNSCC cells 41 and ovarian cancer cells 26 following TGF-␣ antibody treatment. We and others have reported inhibition of cancer cell line growth following treatment with TGF-␣ antisense oligonucleotides or an expression vector in vitro.…”

“…34,56 Previous reports combining TGF-␣ antisense oligonucleotides with an EGFR-specific tyrosine kinase inhibitor or a protein kinase A inhibitor in vitro, suggested that increased growth inhibition could be achieved by targeting the ligand simultaneously with a downstream signaling peptide. 41,57 TGF-␣ antisense oligonucleotides have also been used in conjunction with one of several chemotherapy agents where combined treatment demonstrated increased growth inhibition of colon cancer cells compared with TGF-␣ antisense oligonucleotide alone. 58 Treatments designed to abrogate TGF-␣ production represent a potential means of inhibiting tumor growth in cancers which overexpress this growth factor.…”