SELECTION OF INVASIVE AND METASTATIC SUBPOPULATIONS FROM A HUMAN LUNGADENOCARCINOMA CELL-LINE

To better understand the mechanism(s) underlying lung cancer invasion and metastasis, a Transwell invasion chamber was used to select progre ssively more invasive cancer cell populations from a clonal cell line of human lung adenocarcinoma, CL1. Five sublines with progressive inva siveness, designated CL1-1, CL1-2, CL1-3, CL1-4, and CL1-5, were obtai ned through this in vitro selection process. Their invasive abilities through basement membrane matrix showed a 4- to 6-fold increase over t hat of the parental cells. Moreover, the sublines manifested an increa se in their colony-forming ability on soft agar, tumorigenicity, and m etastatic potency in severe combined immunodeficiency (SCID) mice. Exa mining the phenotypes of the cell lines revealed increased expression of 92 kD gelatinase and an increase in the cell population stained wit h anti-keratin-8 and -18 antibodies. Clonal isolation of anti-keratin- 18-antibody-positive and negative cell populations demonstrated a corr elated enhancement of the invasiveness of these cells and their expres sion of keratin-18. These results support the notion that the metastat ic behavior of lung cancer cells can be characterized with this in vit ro system, and that the properties of these progressively invasive can cer cells can be clonally studied.