The rat Nb2 lymphoma: a novel model for tumor progression.
Tumor progression of cancers is manifested by phenotypic property changes including development of hormone/growth factor independence and metastatic ability. The progression results from acquired genomic alterations leading to clonal heterogeneity and outgrowth of more aggressive and therapy-resistant sublines. Previously, a cultured rat "Nb2 lymphoma" cell line was established, whose viability depends critically on the hormone, prolactin, acting as the principal growth factor. By prolactin starvation, prolactin-independent sublines were generated which possessed the parent karyotype plus extra acquired chromosomal changes (clonal evolution). In this study, the parent line (Nb2-U17) and a cloned subline (SFJCD1) were compared for metastatic ability using single s.c. tumor transplants in Noble rats. Rats (22) bearing Nb2-U17 tumors showed no evidence of metastases at autopsy, even when tumors at implantation site reached a size of 9 cm (length + width). In contrast, rats (19) bearing SFJCD1 tumors showed multiple metastases (liver, kidney) when transplants exceeded 5 cm. This difference in metastatic ability may be related to the acquisition of an inversion in chromosome 1, i.e. inv(1)(q31q41). The 1q41 locus is adjacent to the reported H-ras-1 proto-oncogene locus (1q41-q42). In another subline, tetraploidization (flow cytometric analysis, karyotyping) occurred spontaneously following prolonged culturing (20 mo). Together, the parent Nb2 lymphoma line and its clonal derivatives provide a novel system for studying cellular and molecular mechanisms underlying tumor progression to the metastatic phenotype.
Gout
P W
PW
Department of Cancer Endocrinology, B.C. Cancer Agency, Vancouver, Canada.
Horsman
D E
DE
Fox
K
K
De Jong
G
G
Ma
S
S
Bruchovsky
N
N
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002871:Chromosome Banding; D002999:Clone Cells; D004273:DNA, Neoplasm / Q000032:analysis; D007621:Karyotyping; D007700:Kinetics; D008223:Lymphoma / Q000235:genetics / Q000473:pathology*; D008297:Male; D009362:Neoplasm Metastasis; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm