Acquisition of sensitivity to exogenous fibronectin by friend leukemia cells correlates with reduction of their tumorigenic potential

Abstract

Strongly adhesive, highly flattened clones (FF clones) can be selected from Friend leukemia cells (FLC) cultivated on top of monolayers of human embryonic fibroblasts (HEF). The flattened phenotype of FF clones is stable during cell replication either in soft agar or in vivo. With the number of passages of FLC on HEF the fibronectin (FN) sensitivity of FF clones increases with a proportional reduction of their tumorigenicity. The FN-sensitivity was defined as the ability of a certain dose of FN to flatten 50% of cells of a given FF clone. Tumorigenicity was defined as the number of FF cells able to give palpable tumors, in 50% of inoculated mice. Exogenous FN does not modify the duplication time of FF clones but strongly influences their growth behavior. In the presence of FN, the growth rate of FF cells is controlled by the size of the growth are available. Highly FN-sensitive FF cells grown on FN-coated substrata die at confluency while FF cells not adherent to substrata escape cell death and grow in suspension. We conclude that the high intrinsic FN-sensitivity of FF cells and FN availability at the site of tumor inoculation could be responsible for the reduced tumorigenicity of highly flattened FF clones.

Induction and maintenance of flattened morphology in highly adhesive friend leukemia clones depends on the time‐ and space‐specific assembly of microtubular networks

“…745 A strain of Friend leukemia was routinely maintained in suspension in RPMI 1640, supplemented with 10% fetal calf serum (Gibco, Grand Island, NY) (RPMI). Clone FF 16-1, showing the highest sensitivity to exogenous FN (Benedetto et al, 1982), was grown in RPMI as monolayers in Falcon dishes, precoated with 0.5 pg/cm2 of human plasma FN. Cultures were maintained in 5% C 0 2 humidified atmosphere at 37°C.…”

“…Clone FF 16-1, showing the highest sensitivity to exogenous FN (Benedetto et al, 1982), was grown in RPMI as monolayers in Falcon dishes, precoated with 0.5 pg/cm2 of human plasma FN. Cultures were maintained in 5% C 0 2 humidified atmosphere at 37°C.…”

“…Moreover, FN strongly determined the fate of FF cells growing in vitro: massive cellular death was observed after maximal confluency was reached. The subcutaneous inoculation of FF clones in syngeneic DBA/2 mice clearly showed that the high sensitivity to exogenous FN of FF clones, as appreciated by in vitro studies, correlates well with the reduction of their tumorigenic potential (Benedetto et al, 1982).In the present study, we concentrated our attention on cellular mechanisms actively participating in FNinduced cell adhesion and flattening. We describe the role of microtubules in FN-induced cell spreading and elongation.…”

“…Moreover, FN strongly determined the fate of FF cells growing in vitro: massive cellular death was observed after maximal confluency was reached. The subcutaneous inoculation of FF clones in syngeneic DBA/2 mice clearly showed that the high sensitivity to exogenous FN of FF clones, as appreciated by in vitro studies, correlates well with the reduction of their tumorigenic potential (Benedetto et al, 1982).…”

Reduced maturation of friend virus in adhesive mutants of friend leukemia cells

“…The acquisition of high FN sensitivity by FF clones is accompanied by a proportional reduction of their tumorigenic potential when inoculated in the subcutaneous tissues of DBA/ 2 mice. Cells rescued from tumor masses maintain the flat phenotype and the reduced malignancy, indicating that the altered phenotype is gcnotypically stable (10). For all these reasons FF cell clones can be employed as an useful model to investigate the relationship (ff any) between a fiat, adhesive phenotype and FLV replication.…”