The role of a cell's chromosome complement in its tumorigenic and anchorage independent growth properties in vitro was investigated by injecting a Chinese hamster cell line and its subclones into immunodeficient nude mice and by plating the cells in a semisolid medium containing methylcellulose. The parental WOR 6 cell clone originally consisted of 89% 1s cell and 11% cells with a nearly double (2s) complement. Tumors that developed from WOR 6 were found to consist entirely or primarily of cells with near 2s chromosome complements. Subclones of WOR 6 that contained only 1s cells rarely produced tumors in nude mice, even at high inoculum doses, whereas clones containing a high fraction of 2s cells were consistently tumorigenic. The degree of cellular tumorigenicity thus correlated with cell ploidy. In addition, serial passage of WOR 6 cells in semisolid medium resulted in selective enrichment for near 2s cells and, concomitantly, greatly enhanced tumorigenicity. Analyses of G banded chromosomes revealed that the 1s cells of the WOR 6 parental clone, which has a modal chromosome number of 21 and a range of 18 to 23, is completely or partially monosomic for some chromosomes and trisomic for others. The 2s cells, selected both in vivo through growth as tumors in nude mice and in vitro in semisolid medium, appeared to have resulted from preferential duplication of certain chromosomes of the 1s cell. The results therefore suggest that cells which develop multiple copies of selected genes, while remaining functionally hemizygous for other loci, acquire an enhanced anchorage independent growth potential in vitro an increased tumorigenicity. This conclusion is consistent with the observation that cellular tumorigenicity is correlated with anchorage independence (Freedman and Shin, 1974) and lends support to Ohno's (1974) suggestion that aneuploidy is a possible means employed by cells to express recessive phenotypes and increase their tumorigenicity.
ASJC Scopus subject areas
- Cell Biology