Tumorigenicity of virus-transformed cells in nude mice is correlated specifically with anchorage independent growth in vitro.

Abstract

Clonal isolates of mouse 3T3 cells and primary rat embryo cells, recovered nonselectively after infection by simian virus 40 (SV40), have been tested for tumorigenicity in the immune-deficient nude mice in order to determine the cellular growth properties in vitro specifically correlated with neoplastic growth in vivo. In addition, mouse 3T3 cells transformed by murine sarcoma virus (MuSV, Kirsten strain), and revertants isolated from cells fully transformed by either SV40 or MuSV were also studied. Results suggest that the single cellular property consistently associated with tumorigenicity in nude mice is the acquisition by virus-transformed cells of the ability to proliferate in vitro in the absence of anchorage. Other cellular parameters of virusinduced transformation, such as lack of sensitivity to high cell density and the capacity to grow in low serum concentration, are dissociable from cellular tumorigenicity. This conclusion is supported further by the demonstration that specific selection in vivo for tumorigenic cells from anchorage-dependent cells results in the isolation of anchorage-independent cells. Conversely, a single-step selection in vitro for anchorage-independent cells from nontumorigenic cells results in a simultaneous selection of highly tumorigenic subclones. Infection of susceptible animal cells in vitro by tumor viruses usually results in a spectrum of stable alterations in cellular growth properties, as well as in the appearance of virus-specific antigens in the transformed cells (1). In particular, division in populations of untransformed cells is inhibited by any of the following three environmental constraints: extensive cell-cell contact (2), reduction of serum concentration (3, 4), or deprivation of a solid substrate for cell anchorage (5, 6).Recent results have demonstrated that cellular responses to the experimental parameters which differentiate the normal cell from its transformed counterpart are not coordinately controlled (7,8). Each constraint is the source of a selective assay that yields a different class of transformed cell line. Nonselective transformations of 3T3 mouse cells and of primary rat embryo cells by simian virus 40 (SV40) yielded lines displaying many different transformed phenotypes. While some lines were fully insensitive to each of the three constraints, most transformed lines lost only one or two of these constraints and remained normal for the others. Negative selection of revertant cell lines from a fully transformed 3T3 cell also dissociated these three parameters of growth control (9, 10).These observations suggested to us that not all of the altered cellular growth properties commonly associated with Abbreviations: SV40, simian virus 40; MuSV, murine sarcoma virus, Kirsten strain; RE, rat embryo; ME, mouse embryo. t Present address:

BARX2 and estrogen receptor-α (ESR1) coordinately regulate the production of alternatively spliced ESR1 isoforms and control breast cancer cell growth and invasion

“…Anchorage-independent growth is a hallmark of cellular transformation (Shin et al, 1975). BARX2 induced AIG of MCF7 cells in response to very low estrogen levels, suggesting that it enhanced sensitivity to estrogen.…”

Cell adhesion to the extracellular matrix protein fibronectin modulates radiation-dependent G2 phase arrest involving integrin-linked kinase (ILK) and glycogen synthase kinase-3β (GSK-3β) in vitro

“…Elucidating the process of cell cycle transition that is markedly influenced by irradiation in that cells respond by delaying the cell cycle at checkpoints in the G1-or G2-phase (Lane, 1992;Gadbois et al, 1997;Dimitrijevic-Bussod et al, 1999), additionally showed a regulative role for cell adhesion to ECM (Shin et al, 1975;Hannigan et al, 1996;Kang and Krauss, 1996;Zhu et al, 1996). These checkpoint delays are believed to provide the cell with more time to repair the damage-preserving genome integrity in daughter cells before they continue the division cycle (Little and Nagasawa, 1985;Lane, 1992).…”

“…For the treatment of cells with cytotoxic agents in the presence of ECM, the convergence of integrin-related and cell cycle-related signal transduction pathways could be of great importance. Possible interactions of these pathways are likely to be modulated by the ECM and, thus, may play an important role in resistance-mediating mechanisms (Sethi et al, 1999;Hazlehurst et al, 2000), anchorage-independent cell growth (Shin et al, 1975;Radeva et al, 1997), oncogenic transformation (White et al, 2001), the assessment of in vitro cytotoxicity studies, and new strategies for controlling and healing cancer.…”

Comparison of cell-surface glycoproteins of rat hepatomas and embryonic rat liver

“…However, more extended studies have recently shown that these phenomena are 11 not, or are not generally, characteristic of tumourigenic cells (Kolata, 1975;Shin et al, 1975;Hynes, 1976;Nicolson, 1976;Shields, 1976;Smets, Van Beek and Van Rooij, 1976;Nilsson et al, 1977). These findings underline the importance of extending investigations to several cell systems.…”