Characterization of two cell lines with distinct phenotypes established from a patient with small cell lung cancer

Abstract

Two small cell lung cancer (SCLC) cell lines were established from pericardia! and pleura! effusions of a patient with histopathologically proven SCLC of the oat cell type. Chemotherapy was administered without response during the 148-day period prior to the establishment of the first cell line, SCLC-22H, and some of the same drugs were admin istered in the 15 days prior to the establishment of the second cell line, SCLC-21H. Both cell lines differed markedly in their biochemical, kinetic, and morphological properties. Although the biomarkers i -Dopa decarboxylase, bombesin, carcinoembryonic antigen, and neurotensin were detectable in SCLC-22H, they were undetectable or low in SCLC-21H. The population doubling time was twice as fast and the colony forming efficiency higher in S( IX -2111 than in SCLC-22H. They both expressed high concentrations of the SCLC marker enzymes neuronspecific enolase and the creatine kinase isoenzyme BB and showed no significant differences in their chromosomal characteristics, c-myc was amplified and expressed in both cell lines, and SCLC-21H had an additional rearrangedand amplified EcoKl c-myc fragment. Morpholog ical differences were apparent in liquid culture, cytology, and xenograft histology, SCLC-21H grew much more loosely than SCLC-22H, and had more prominentnucleoli and more abundantcytoplasm. Ultrastructurally dense core granules were present in both cell lines. SCLC-21H thus expressed properties of the variant cell type of SCLC, whereas SCLC-22H had mixed classic/variant features. An in viro progression of the patient's tumor from a pure small cell to a mixed small cell/large cell morphology could be demonstrated, which suggests that cell line SCLC-22H represents a cell type characteristic for the transitional phase of the tumor. The features of this cell line therefore define a new subclass of SCLC called transitional cell type. SCLC-22H may be of use to study the mechanisms involved in the classic to variant transition, which probably has a considerable impact on the prognosis and response to therapy.