HETEROTRANSPLANTATION OF HUMAN BURKITTS-LYMPHOMA CELL-LINES IN ATHYMIC NUDE-MICE - TUMOR-HOST RELATIONSHIPS

We have explored the factors which influence tumorigenicity of Burkitt's lymphoma (BL) cell lines in athymic nude mice. Four cell lines, Namalwa, CA46, JD38, and ST486 revealed tumor incidence of 63.5, 69.0, 45.5 and 10.0%, respectively, in nude mice, but there was no correlation between tumor incidence and growth rate in vivo. Thus, growth rate and tumorigenicity are dependent upon different biochemical pathways. Evidence of tumor cell heterogeneity was demonstrated in the CA46 parent cell line. Five subclones derived from CA46 revealed varying degrees of tumor incidence (but very similar growth rates) that were consistently less than the parent CA46 line. Line 5, for example, produced 5.7-fold less tumors than the parent line. None of the BL cell lines or clones produced any metastatic lesions in liver, lung, brain, bone marrow or spleen in athymic nude mice. Northern blot analysis of c-myc mRNA levels in different BL cell lines revealed a possible relationship between percent tumor takes (but not growth rates) and the level of c-myc oncogene expression. However, no correlation was observed between c-myc mRNA levels and tumor incidence or growth rates among the CA46 clones. There was no correlation between the ability of the cell lines and the subclones to either secrete growth factors or to respond to growth factors secreted by Epstein-Barr virus-induced lymphoblastoid cells or lipopolysaccharide-activated monocytes, and their growth rates or percent tumor takes in mice. Comparison of tumor incidence and growth rates in irradiated and unirradiated mice showed that host factors influenced the growth of BL in nude mice. Tumor heterotransplantation after whole-body X-irradiation of the mice resulted in an increase in tumor incidence in 4 of 5 lines injected. At 2 weeks after cell inoculation, subclone 5 (CA46) had a 100% tumor take in irradiated mice, whereas in untreated mice the incidence was 0%. The appearance of large tumors at this early time point also indicated an increase in growth rate. However, the lack of an increase in tumor incidence after irradiation in one cell line (ST486) strongly suggests that the interaction of tumor cell characteristics, probably surface characteristics, with host factors is required for BL growth in nude mice.