Characterization of Variant Subclasses of Cell Lines Derived from Small Cell Lung Cancer Having Distinctive Biochemical, Morphological, and Growth Properties1

We have described the establishment and biochemical char acterization of 50 small cell lung carcinoma (SCLC) cell lines. Further analysis of these data, combined with studies of mor phology and growth characteristics, indicates that 35 (70%) of the lines retained typical morphology (SCLC, intermediate sub type), growth characteristics (growth as tightly packed floating cellular aggregates, long doubling times and low colony-forming efficiencies), and biochemical profile (presence of L-dopa decarboxylase, bombesin-like immunoreactivity, neuron-specific enolase, and high concentrations of brain isoenzyme of creatine kinase). They are referred to as classic SCLC lines. The remain ing 15 (30%) lines had discordant expression of the biochemical markers; they retained high concentrations of brain isozyme of creatine kinase, but had significantly lower concentrations of neuron-specific enolase and lacked L-dopa decarboxylase and bombesin-like immunoreactivity. These cell lines are called var iants. SCLC variant lines could further be divided into (a) bio chemical variant lines having variant biochemical profile but re taining typical SCLC morphology and growth characteristics; and (b) morphological variant (SCLC-MV) lines having variant biochemical profile, altered morphology (features of large cell undifferentiated carcinoma) and altered growth characteristics (growth as loosely attached floating aggregates, relatively short doubling times and cloning efficiencies). Fifty-five clones derived from the three SCLC subclasses retained their parental phenotypes. In SCLC-MV lines there was a near constant relationship between variant morphology, altered growth characteristics and amplification of the c-myc oncogene; classic SCLC and biochem ical variant SCLC lines were not amplified. Variant morphologies frequently are present in SCLC tumors at autopsy, and most SCLC-MV lines reflect changes that had occurred in the tumors from which they were derived. Because SCLC-MV tumors be have more virulently in the patient and are radioresistant in vitro, these findings are of considerable biological and clinical interest.