1987 Volume 33 Issue 4 Pages 683-700
The role of Epidermal Growth Factor (EGF) and the expression of its receptor in human squamous cell carcinomas (SCC) were studied. EGF was found to inhibit the growth of 14 cell lines derived from SCC of the oral cavity, skin, esophagus and vulva, at doses that stimulated the growth of epidermal keratinocytes and dermal fibroblasts. However, EGF did not inhibit the growth of other tumor cells, such as adenocarcinomas of the stomach, cervix, and breast and sarcomas.
The number of EGF receptors on SCC cells were measured by immunoprecipitation of labeled proteins with anti-EGF receptor polyclonal antibody and binding assay of membrane preparations using 125I-EGF. Of 13 SCC cell cultures tested, all except 3 of esophageal SCC showed to 50 times higher level of EGF receptors than normal epidermal keratinocytes. The values of the equilibrium dissociation constant (Kd) of these cells were on the order of nM.
The sensitivity to the growth inhibitory effect of EGF correlated well with the elevated level of EGF receptors in 12 SCC cell lines.
By use of two murine monoclonal antibodies (528 IgG, B4G7) which react with the binding domain of human EGF receptor, EGF receptors were immunostained. All of the SCC cell cultures showed strong staining at their membrane, in contrast, normal fibroblasts showed no staining. In immunohistological study, all of the SCC tissues showed strong staining of EGF receptor without staining of their cancer pearl. In normal epithelium of skin and oral mucosae, positive staining was found in the basal layer and no staining in the keratinized layer.
Southern blot hybridization of DNAs from 7 SCC cell lines demonstrated amplification of EGF receptor/c-erbB gene. In contrast, DNAs of primary tumors of 4 SCC and 1 mucoepidermoid tumor showed no amplification of EGF receptor/c-erbB gene. Besides EGF receptor gene, no amplification of c-H-ras, c-src, c-fos, c-K-ras was found. However, amplification of c-myc was detected in some SCC cell lines and 2 primary tumors of SCC.
These results suggest that EGF and EGF receptors play a role in the development of SCCs, and over-expression of EGF receptor has high incidence in SCC cell lines resulting from amplification of its gene. In addition, cells with an amplified EGF receptor gene may more readily adapt to growth in tissue culture, and the detection of EGF receptor may histologically be a useful tool as a tumor marker of SCC.