Malignant progression of rat Nb2 lymphoma cells: chromosomal alterations and metastatic properties.
Cultured rat pre-T Nb2 lymphoma cell lines have provided a useful model for tumor progression of T-cell cancers. Comparative analysis of the non-metastatic, prolactin (PRL)-dependent parental Nb2-U17 line and its PRL-independent and/or metastatic sublines, can be used in a search for progression-related genomic alterations. In the present study, the PRL-dependent, cloned Nb2-11C and PRL-independent Nb2-Sp sublines were used to examine development of metastatic ability and PRL independence relative to chromosomal alterations. Metastatic ability was determined using Noble rats carrying subcutaneous tumor transplants; PRL dependence/autonomy was checked in culture. Nb2-11C tumor transplants quickly gave rise to morbidity, associated with metastases in kidney and liver. Transplants of the slower growing Nb2-Sp cells showed variable tumorigenicity as metastases developed in only 40% of the rats (in lungs, kidney, stomach). G-banded chromosome analysis showed the Nb2-11C culture had the karyotype of the parental Nb2-U17 line plus an extra chromosome 19, thus, indicating an association between the development of metastatic ability in Nb2-11C cells and trisomy 19. The Nb2-Sp subline was not clonal. Its stemline showed two alterations in the parental karyotype: acquisition of an add(7)(q10) and loss of the extra chromosome add(15)(p12). Additional abnormalities, add(6)(q11) and trisomy 19, occurred in 15% and 5% of the Nb2-Sp population, respectively. Passaging of the Nb2-Sp subline in vivo resulted in generation and/or outgrowth of new sublines, a major one of which showed an apparent transient growth requirement for lactogens. Possible mechanisms underlying the PRL independence and in vivo properties of the Nb2-Sp cells are discussed.
Too
C K
CK
Department of Biochemistry, Dalhousie University, Halifax, Nova Scotia, Canada.
Lee
C
C
Sangster
S M
SM
Gout
P W
PW
D000818:Animals; D015197:Carcinogenicity Tests; D002455:Cell Division / Q000235:genetics; D002869:Chromosome Aberrations; D003470:Culture Media; D007621:Karyotyping; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009362:Neoplasm Metastasis / Q000235:genetics; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D014314:Trisomy; D014407:Tumor Cells, Cultured
D003470:Culture Media; D011388:Prolactin