AN ENHANCED AND SENSITIVE AUTOCRINE STIMULATION BY TRANSFORMING GROWTH-FACTOR-ALPHA IS ACQUIRED IN THE BRAIN METASTATIC VARIANT OF A HUMAN NON-SMALL-CELL LUNG-CANCER CELL-LINE

Transforming growth factor-alpha (TGF-alpha)-mediated autocrine regula tion in human non-small-cell lung cancer (NSCLC) cells NCI-H226 and it s brain metastatic variant H226Br were compared. An enhanced TGF-alpha -induced dose-dependent mitogenic responsiveness in H226Br cells was o bserved. Neutralising antibody that binds TGF-alpha inhibits H226Br ce ll growth more effectively than NCI-H226 cell growth. Binding assay wi th I-125-labelled epidermal growth factor (EGF) revealed that H226Br h as two types of EGF receptors (EGFRs), whereas the parental cell line, NCI-H226, has only one. H226Br cells contain twice as many EGFRs as H 226 cells, as proved by Scatchard analysis and immune kinase assay. No rthern analysis indicated that there is more EGFR transcript in H226Br than in NCI-H226, indicating a transcriptional EGFR gene elevation du ring metastasis progression. The level of accumulated immunoactive TGF -alpha is lower in the conditioned medium of H226Br than in that of NC I-H226, demonstrating down-regulation of TGF-alpha transcript. The acc umulated data suggest an elevated and sensitive autocrine modulation b y TGF-alpha and EGFR in immortalising the brain metastatic variant cel ls that were derived from a human NSCLC squamous cell line.