THE RAT NB2 LYMPHOMA - A NOVEL MODEL FOR TUMOR PROGRESSION

Tumor progression of cancers is manifested by phenotypic property chan ges, including development of hormone/growth factor independence and m etastatic ability. The progression results from acquired genomic alter ations leading to clonal heterogeneity and outgrowth of more aggressiv e and therapy-resistant sublines. Previously, a cultured rat ''Nb2 lym phoma'' cell line was established whose viability depends critically o n the hormone prolactin, acting as the principal growth factor: By pro lactin 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 cl oned subline (SFJCD1) were compared for metastatic ability using singl e sc. tumor transplants in Noble rats. Rats (22) bearing Nb2-U17 armor s showed no evidence of metastases at autopsy, even when tumors at imp lantation site reached a size of 9 cm (length + width). In contrast, m rs (19) bearing SFJCD1 tumors showed multiple metastases (liver kidney ) when transplants exceeded 5 cm. This difference in metastatic abilit y 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, tetraploidizatio n (flow cytometric analysis karyotyping) occurred spontaneously follow ing prolonged culturing (20 mo) Together; the parent Nb2 lymphoma line and its clonal derivatives provide a novel system for studying cellul ar and molecular mechanisms underlying tumor progression to the metast atic phenotype.