The purpose of this study was to determine whether the growth of human
melanoma cells in the brain parenchyma is selective and represents th
e growth of unique cells. Six human melanoma cell lines derived from c
utaneous lymph node or brain metastases (from six different patients)
and melanoma cells isolated from fresh surgical specimens of two prima
ry cutaneous melanomas, two lymph node metastases end two brain metast
ases (each from a different patient) were injected into the subarachno
id space of nude mice. All melanomas produced growths in the leptomeni
nges, but only melanoma cells isolated from brain metastases infiltrat
ed into and grew in the brain parenchyma of nude mice. The results fro
m in vitro assays for cell motility or production of gelatinase activi
ty did not correlate with in vivo growth pattern. However, the in vitr
o growth of human melanoma cells in the presence of TGF-beta(2) invers
ely correlated with potential for brain parenchyma metastasis, i.e. th
e growth of cells from brain metastases was least inhibited by TGF-bet
a(2). These data suggest that melanoma brain parenchyma metastases are
produced by unique cells that may be resistant to the antiproliferati
ve effects of TGF-beta(2).