Suppression of tumorigenicity in somatic cell hybrids

Abstract

Cell hybrids between nontumorigenic human diploid and tumorigenic heteroploid cells of the D98AH2 strain initially contain a complete or nearly complete chromosome complement of both parental lines. Of 35 such independent isolates all failed to form tumors when inoculated at 146 different sites in nude mice, even at cell doses 40 fold greater than those at which D98AH2 cells produce tumors. This agrees with observations of others in similar intraspecific systems. These hybrids remained nontumorigenic after subcloning and prolonged culture. However, they had not lost their tumorigenic potential since tumorigenic isolates could be recovered at a low incidence either by selecting in semisolid medium or by backselecting in 6-thioguanine supplemented medium. These tumorigenic isolates had lost chromosomes, primarily those of the diploid parent, suggesting that these chromosomes convey the suppressor information. Only specific chromosomes can carry such information, since other isolates with equally low chromosome numbers were not tumorigenic. A series of cell phenotypes often found in tumorigenic cells, such as infinite life span, anchorage independence, loss of contact inhibition, decreased fibronectin production, and ability to grow at low serum concentration, were found to segregate independently of tumorigenicity, clearly indicating that they are under separate control and that they are not cell properties that by themselves, or in concert, are essential for the tumorigenic phenotype. This agrees with observations of others. However, there was some indication that these characters may potentiate tumorigenicity.