CELL-SUBSTRATUM INTERACTIONS MEDIATE ONCOGENE-INDUCED PHENOTYPE OF LUNG-CANCER CELLS

In vivo and in vitro studies have linked small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) cells along a differentiation continuum, The transition of a SCLC toward a NSCLC phenotype is modele d in culture by the simultaneous overexpression of myc and ras genes i n cultured SCLC cells. A major phenotypic distinction between SCLC and NSCLC in culture is that SCLC cells usually grow in floating aggregat es, whereas NSCLC cells and myc- plus ras-expressing SCLC cells grow a s adherent spreading monolayers like other epithelial cells, The prese nt studies examine how myc, ras, cell aggregation, and attachment to l aminin may interact to modulate transitions between the SCLC and NSCLC phenotypes, We find that myc-expressing SCLC cells, which normally gr ow as anchorage-independent cells in plastic flasks, will adhere to la minin and exhibit an epithelial morphology, In this setting, the cells express both NSCLC and SCLC markers, thus resembling a tumor type pre viously termed NSCLC with neuroendocrine features, Anchorage-dependent SCLC cells simultaneously expressing the myc family and an exogenous ras oncogene move further toward the NSCLC phenotype than the above my c-expressing cells, However, forced suspension of such cells restores the expression of neuroendocrine SCLC features, These studies indicate that cell environment, as much as gene expression events, profoundly affects aspects of the SCLC cell phenotype.