| Abstract |
The malignant potential of neoplastic or transformed cells correlates with
their ability to multiply to a high saturation density in vitro. This
property has been demonstrated in a number of syngeneic mouse and hamster
cell-host systems. In human work, tests for tumorigenicity must
necessarily be indirect, since autologous and allogeneic transplantation
experiments are precluded by ethical considerations. The ability of a
given population of human cells to grow as a solid hetero-transplant in
immunologically privileged sites or immuno-deprived hosts of rodent origin
seems to reflect their malignant potential. With the definition of a
marked deficiency of thymus-dependent immune function in the congenitally
athymic nude mice, this model has been widely used for
heterotransplantation and chemotherapy studies of human tumors. A number
of human tumor biopsies and cultured cells including malignant melanoma
have been successfully transplanted to nude mice. Some attempts have been
made to correlate heterotransplantability of virally transformed human
fibroblastic cells or human cell lines of both neoplastic and non-
neoplastic origin, with their in vitro growth characteristics. To our
knowledge, however, no quantitative studies by a more analytical approach
have been reported to confirm such correlation in human tumor cells.
We have recently investigated seven well-characterized human melanoma cell
lines in terms of their transplantability in the cheek pouch of the
cortisonized hamster and have found no correlation between
heterotransplantability and saturation density, although progressive in
vivo growth was noted only among the melanoma lines which were grossly
pigmented. Within heterogeneous cell populations, there may be variable
expression of a common genotype depending on the relative influence of the
prevalent selective pressures. Thus, in an uncloned population the ability
to grow as a xenograft may be predominantly manifest by certain
subpopulations while the in vitro growth potential may be more dependent
on different subpopulations. Therefore, in the present study we used
clonal sublines of a human melanoma line to reexamine whether any
relationship exists between saturation density and tumorigenicity.
Tumorigenicity (malignant potential) was determined by tumor production in
nude mice.
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