EXPRESSION OF EPIDERMAL AND NERVE GROWTH-FACTOR RECEPTORS AND SOFT AGAR GROWTH-FACTOR PRODUCTION BY HUMAN-LUNG CANCER-CELLS

Abstract

Seventeen well-characterized human lung cancer cell lines were examined for the presence of specific membrane receptors for epidermal growth factor (EGF) and nerve growth factor (NGF) as well as for the production of diffusible factors capable of stimulating soft agar growth. These cell lines represented all 4 major histological types of human lung cancer including small cell carcinoma of the lung (SCCL) and the 3 types of non-SCCL (epidermoid, large cell and adenocarcinoma). The SCCL lines included 3 lines referred to as converters because they had lost SCCL morphological and biochemical properties during prolonged passage in vitro. Specific receptors for EGF and NGF were detected by measuring the binding of 125I-radiolabeled growth factor to the cell surface. These assays revealed that EGF receptors are found on 5 of 6 non-SCCL cell lines and are not found on any of the SCCL lines. NGF binding was detected at low levels on 3 of 8 SCCL lines and on all 3 SCCL converters but was not observed for non-SCCL lines. Thus, SCCL and SCCL converter cell lines are distinguished from non-SCCL by the pattern of membrane receptors for EGF and NGF. Such differences may ultimately prove useful as biological markers for the different histological types of lung cancer. The majority of SCCL cells and all of the non-SCCL cells tested produced diffusible growth factors which can stimulate soft agar growth of nontransformed normal rat kidney fibroblasts. Although some correlation between soft agar growth factor production and the absence of EGF receptors may exist for SCCL cells, the production of transforming growth factors appears to be a general property of human lung cancer cells in vitro and is independent of EGF receptor expression.