TUMOR FORMATION BY TRANSFORMED CELLS IN NUDE MICE

Abstract

Malignant transformation of animal cells in vitro involves changes in many cellular properties, but most of these can be dissociated from malignant growth potential in vivo. Earlier studies showed that anchorage independent growth, defined as the ability of cells to proliferate without attachment to the tissue culture plate, is specifically correlated with tumor-forming ability in nude mice. Since viral transformation of rodent cells in vitro is associated with decreased organization of the actin-containing microfilament bundles and with loss of the cell surface glycoprotein fibronectin (FN), we examined whether the acquisition of anchorage independence is related to these cytoskeletal changes. A variety of primary cell strains and established cell lines were screened for the associations among tumorigenicity, anchorage independence, and loss of FN. We also isolated (from a nontransformed hamster line, NIL8) a series of mutants with alterations in one of these phenotypes and then examined them for concomitant changes in the other properties. Our results indicate that there is no specific association between loss of FN and either cellular tumorigenicity or anchorage independence, and therefore, that loss of the anchorage requirement cannot be explained on this basis. In contrast, loss of actin cables was coordinately induced in NIL8 cells selected for anchorage independence in vitro or for tumorigenicity in vivo.;Primate cells transformed in vitro by SV40 to the anchorage independent state rarely form tumors in nude mice, and therefore constitute an important exception to the otherwise tight correlation between anchorage independence and cellular tumorigenicity. In order to determine whether the failure of these cells to grow in nude mice is due to active host suppression, we injected 2 anchorage independent clones of SV40-transformed human cells (SV80 and GM0639) into nude mice which also lacked other immune functions {lcub}natural killer (NK) or T-independent B cells{rcub}. No tumors were found in the NK-deficient hosts, but one SV80 tumor grew in a T- and B-cell-deficient (CBA/N nude) mouse. When these tumor cells were recovered and reinjected into hosts with multiple immune deficiencies, they also formed tumors at a low incidence only in CBA/N nude mice. These results suggest that some SV40-transformed human cells are inherently neoplastic and that their failure to grow in nude mice is at least partly due to a thymus-independent tumor rejection mechanism present in this host.