Cellular behavior of metastatic B16 melanoma in experimental blood-borne implantation and cerebral invasion. An electron microscopic study

Abstract

Using B16 melanoma variant subline B16-B14b, which was selected in vivo for enhanced brain surface colonization abilities in C57BL/6 mice, we have examined ultrastructurally the cellular behavior of B16 melanoma cells during the process of cerebral invasion. Within 14 days after the injection of viable tumor cells (10(5) cells/0.2 ml) into the common carotid artery, gross nodular tumors were identifiable in the cerebral cortex. Tumor cells in the boundary area of the cerebral cortex and leptomeninges breached the limiting glial membrane with numerous small cytoplasmic protrusions and invaded into the brain parenchyma by direct extension or along blood vessels. Direct invasion into the brain parenchyma was characterized by two ultrastructural features of the tumor cells: the production of many elongated cytoplasmic protrusions at zones of invasion which separated, fragmented, and eventually engulfed nervous tissue; and the formation of tumor cell attachments to the dendrites of nerve cells via tight junction-like structures. Another mechanism of brain parenchyma infiltration by the melanoma cells was invasion and migration along blood vessel walls of the cerebral capillaries. In this case B16 melanoma cells were found attached directly to the basolateral side of the blood vessel basal lamina. The tumor cells appeared to achieve their basal lamina location by pushing aside the perivascular astrocytes.