Brain surface invasion and metastasis of murine malignant melanoma variants

Abstract

Mouse B16 melanoma sublines were selected sequentially for their abilities to colonize brain meninges and leptomeninges of C57BL/6 mice. After 14 selections subline B16-B14b was established that formed significantly more brain tumor colonies than the parental B16 line. Examination of brains at various times after intravenous or intra-arterial injection of B16 cells by electron microscopy revealed that B14b melanoma cells lodged in small brain blood vessels, proliferated and invaded through vessel walls into brain parenchyma and also along small blood vessels at perivascular sites. Invasion into brain parenchyma was characterized by extension of melanoma cell filopodia resulting in fragmentation and sometimes enfulgment of glial and neural cells. Analysis of cell surface proteins of B16 melanoma sublines revealed increased exposure of a Mr approximately 90,000 glycoprotein on the high brain-colonizing cells. Antibodies against the Mr approximately 90,000 glycoprotein reacted with a variety of human melanoma cell lines and with some fetal and adult tissues, indicating that this melanoma-associated component is not species-, tumor- or tissue-specific. The glycoprotein could be a cell surface receptor important in the survival and growth properties of melanoma cells in brain microenvironments.