Growth properties, differentiation capacity and oncogene expression in metastatic and nonmetastatic Friend leukemia cell variants.
The aims of this study were: (1) to characterize the biologic properties of the WGA-resistant (WR) Friend leukemia cells (FLC) as compared to the original nonmetastatic or highly metastatic FLC; (2) to investigate the possible correlations between the expression of some oncogenes (i.e., c-myc, H-ras and K-ras) and the in vitro and in vivo behavior of FLC. The tumorigenic behavior of the different FLC types strongly depended on the site of tumor injection. Both WR FLC and in vitro passaged FLC did not grow as ascites (when injected intraperitoneally) and developed large solid tumors (when injected subcutaneously), without forming any spleen or liver metastasis. In contrast, in vivo passaged FLC rapidly formed hemorrhagic ascites when injected intraperitoneally; the subcutaneous injection of these cells resulted in the development of solid tumors, which were smaller than the other FLC tumors, but capable of metastasizing to the liver and to the spleen. No significant differences were observed in the in vitro growth characteristics and cell cycle parameters among the different FLC types under various experimental conditions (i.e., FCS concentration or cell seeding densities). Similarly to the metastatic in vivo passaged parental cells, WR FLC exhibited a much lower erythroid differentiation after in vitro addition of either dimethyl sulfoxide or hexamethylene bisacetamide than the in vitro passaged FLC. High levels of c-myc oncogene mRNA were expressed in all FLC variants; no major variations in the c-myc expression were observed in FLC cultivated in medium supplemented with different FCS concentrations and/or seeded at various cell densities. In addition, no changes in the expression of H-ras or K-ras were observed between the different FLC types.
Sala
A
A
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
Benedetto
A
A
Elia
G
G
Pulciani
S
S
Ciotta
C
C
Parlanti
E
E
Santodonato
L
L
Belardelli
F
F
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005622:Friend murine leukemia virus; D016259:Genes, myc; D011905:Genes, ras; D006410:Hematopoiesis; D066298:In Vitro Techniques; D007942:Leukemia, Experimental / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008811:Mice, Inbred DBA; D009362:Neoplasm Metastasis; D009857:Oncogenes; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics
D000081:Acetamides; D016283:Proto-Oncogene Proteins p21(ras); C014026:hexamethylene bisacetamide; D004121:Dimethyl Sulfoxide