Human cell hybrids derived from malignant HeLa and normal fibroblast parental cells expressed man of the transformed properties of the HeLa parent but their tumor-producing capability was suppressed. Hybrids derived from HeLa/HeLa fusions retained both their transformed and malignant henotypes. Thus, an apparent separation of the control of the transformed versus malignant phenotype is indicated. Furthermore, several transformed properties-including lack of density-dependent inhibition of growth, lectin agglutination, lowered requirement for serum growth factors, and anchorage independence-are expressed coordinately in the nontumorigenic hybrids. This finding suggests that none of these properties by themselves, or in concert, endows a cell with tumorigenic potential.The transition of a normal cell to a neoplastic one is reflected by a complex array of phenotype changes that are amenable to study. Many of these changes-which include lack of contact inhibition of division or topoinhibition (1, 2), reduced requirement for serum growth factors (3, 4), agglutination of cells by lectins (5, 6), anchorage independence (7, 8), altered cyclic nucleotide levels (9, 10), increased protease activity (11), and surface membrane changes such as altered ganglioside profiles (12) and fluctuations in the expression of glycoproteins [e.g., large external transformation sensitive glycoprotein (LETS)] (13, 14)-have been the subjects of intense investigation. Apparent correlations between one or more of these properties and the neoplastic (malignant) state of transformed* cells have been suggested (3-18), but in most cases the dependence of the malignant state on any one of these properties has been questioned (19)(20)(21)(22). In many of these investigations, cells of differing origins, including different animal species, have been used for comparative purposes.We report here our findings with intraspecific human hybrids, in which malignancy (defined here as the capacity of cells to produce a progressively growing tumor in a suitable host) is suppressed, whereas many of the in vitro properties that have been associated with malignant transformation continue to be expressed. Our results indicate that these two functional states-that is, the malignant and transformed phenotypes-are under separate genetic control in this cell system.
MATERIALS AND METHODSParental and Hybrid Cells. The parental and hybrid cell lines are presented in Table 1. Details of hybridization procedure and selection of hybrids have been presented elsewhere (23). All cell populations were regularly tested for the presence of mycoplasma contaminants by cultural methods, uridine/ uracil ratio (24), and 4',6-diamidino-2-phenylindole assay (25).The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertuement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.The only cell line that was contaminated with mycoplasmas was ESH6.Growth Curves. Topoinhibition wa...