Inhibition of Growth of Human Lung Adenocarcinoma Cell Lines by Anti-Transforming Growth Factor-  Monoclonal Antibody

Abstract

We previously reported that two human lung adenocarcinoma cell lines (A-549 and PC-9) produce human transforming growth factor-alpha (hTGF-alpha) and express its receptors. In the present study an exogenously added monoclonal antibody against recombinant hTGF-alpha inhibited growth of these cell lines in vitro. This result indicated that endogenous hTGF-alpha produced by the cancer cells can function as an autocrine growth factor.

The relationship of quantitative epidermal growth factor receptor expression in non-small cell lung cancer to long term survival

“…TGFa binds to the EGFr with similar actions to those on binding of EGF with its receptor (Reynolds et al, 1981). Imanishi et al showed that an exogenously added monoclonal antibody against hTGFa inhibited growth of hTGFa producing lung adenocarcinoma cell lines in vitro (Imanishi et al, 1989).…”

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

“…33 Previous therapeutic approaches designed to abrogate TGF-␣ in vitro have included the use of neutralizing antibodies or antisense oligonucleotides. 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.…”

The EGF/TGFα response element within the TGFα promoter consists of a multi-complex regulatory element

“…The importance of EGFr activation in the regulation of TGFa, either by EGF or TGFa itself, has been established by the use of EGFr antibodies (Markowitz et al, 1990;Ennis et al, 1989;Imanishi et al, 1989). Although the TGFa promoter has been isolated, little is known about the mechanism of response to EGFr activation.…”

“…The use of neutralizing antibodies to both TGFa and the EGFr, and TGFa antisense approaches have all demonstrated that TGFa is an autocrine growthstimulatory factor in colon carcinoma (Markowitz et al, 1990;Burgess, 1991, 1992;Ziober et al, 1993) as well as other tumors Ennis et al, 1989;Imanishi et al, 1989;Malden et al, 1989;Lee et al, 1991). TGFa has also been shown to be an autocrine growth factor in normal cells (Markowitz et al, 1990;Malden et al, 1989;Co ey et al, 1987;Madtes et al, 1988;Bates et al, 1990;Kudlow and Bjorge, 1990;Lewis et al, 1990) and during development (Wilcox and Derynck, 1988).…”

“…Increased TGFa protein secretion into culture media is also observed with similar kinetics. Activation of the EGFr has been implicated in this autoinduction as neutralizing antibodies to EGFr inhibit both TGFa accumulation into the media and the growth of many types of tumor cells in vitro (Markowitz et al, 1990;Ennis et al, 1989;Imanishi et al, 1989). Furthermore, overexpression of TGFa in the weakly tumorigenic colon carcinoma cell line GEO by stable transfection of a TGFa expression vector resulted in the isolation of clones with increased tumorigenicity both in vitro and in vivo (Ziober et al, 1993).…”