ORGAN-SPECIFIC METASTASES IN IMMUNODEFICIENT MICE INJECTED WITH HUMAN-MELANOMA CELLS - A QUANTITATIVE PATHOLOGICAL ANALYSIS

Pathological and morphometric techniques were used to investigate the potential of two human melanoma cell lines for organ colonization in t hree different immunodeficient mouse strains; nude (nu/nu), NIH triple immunodeficient (TID: nu/nu, bg/bg, xid/xid) and severe combined immu nodeficient (SCID) mice. The MM-RU cell line gave rise exclusively to lung metastases, whereas the MM-AN cell line gave rise to lung and ext rapulmonary metastases. Although the TID mice showed more pancreatic a nd brown fat lesions than nude or SCID mice, the overall pattern of di stribution of organ metastases among the strains was similar, suggesti ng that cellular properties intrinsic to the melanoma cells are import ant for the colonization of specific organs. The metastatic nodules we re well circumscribed in all organs and exhibited peripherally located macrophages, except for brain metastases, where a more invasive patte rn along vasculature was observed. The differences in cellular infiltr ate and infiltrative patterns of the tumors implicate features of the host microenvironment (organ-specific factors) which are, at least in part, independent of the host's genetic background or degree of immuno deficiency. Our findings suggest that intrinsic malignant cellular pro perties play an important role in organ-specific colonization by haema togenously metastasizing cells.