The pattern of metastasis of human melanoma to the central nervous system is not influenced by integrin alpha(v)beta(3) expression

We investigated the effect of integrin alpha (v)beta (3) expression on the metastatic pattern of human melanoma cells in the central nervous system (C NS). For this purpose, we developed a hematogenous CNS melanoma metastasis model in nude mice using a modified internal carotid artery infusion techni que. This protocol revealed 2 different patterns of CNS metastasis. The int egrin alpha (v)beta (3)-expressing melanoma lines Me157 and Zkr nearly excl usively produced metastases in the brain parenchyma, whereas cells of the B LM and MV3 lines, devoid of integrin alpha (v)beta (3) expression, preferen tially metastasized to dura mater and leptomeninges. Treatment with hyaluro nidase to obtain single BLM cell suspensions did not influence the metastat ic pattern, indicating that this was not simply the result of entrapment of tumor cell aggregates in large-sized leptomeningeal vessels. The role of i ntegrin alpha (v)beta (3) expression in the process of metastasis was teste d by transfection of BLM, but did not lead to an altered pattern of metasta sis. We did observe, however, slower growth of the transfected tumors, alth ough the in vitro growth rate was unaltered, indicating a reduction in tumo rigenicity, We conclude from our findings that CNS metastasis of melanoma c ells in the mouse xenograft model occurs in at least 2 different but very r eproducible patterns. Although it is predicted that adhesion of tumor cells to endothelial cells plays a role in this phenomenon, tumor cell integrin alpha (v)beta (3) expression per se does not explain the difference in meta static behavior in the CNS. We assume that other, as yet unknown factors, m ust be involved. (C) 2001 Wiley-Liss, Inc.