Invasiveness in primary intracranial tumors: Part 2. Studies with scanning electron microscopy of cell surface alterations associated with invasiveness.

We previously described an experimental model for the production of invasive and noninvasive astrocytic series tumors and a semiquantitative assessment of their invasiveness. The tumors are produced by intracerebral inoculation of simian virus 40-transformed cells from four different brain regions. Cells of cerebral cortex and brain stem derivation produced invasive tumors; tumors of cerebral cortex derivation were more invasive and became increasingly invasive with alternate in vivo and in vitro passage. Cells of cerebellar hemisphere and vermis derivation produced primarily noninvasive tumors. This report describes the surface configuration of these tumor cells in culture at or near confluence as visualized with scanning electron microscopy. Normal cells form a multilayered base of flat, overlapping cells with few excrescences and indistinct borders and have only rare dividing or giant cells attached. Invasive tumor cells from a monolayer base of extremely flat and spread out cells almost devoid of excrescences, with few dividing or giant cells attached. Cells of cerebral cortex derivation additionally have numerous microvilli and ruffles at points of intercellular contact and become covered with microvilli after passage. These features were retained after cloning by dilution plating, but not after cloning by growth in soft agar. Our primarily noninvasive cells form a multilayered base of rounded cells covered with various excrescences and numerous attached dividing and giant cells. These surface features seem to be related to intercellular and cell-substrate adherence. The configuration of the invasive cells is consistent with increased cell-substrate adherence, substrate-dependent inhibition of locomotion, and decreased intercellular adherence among the more invasive cells. The configuration of our primarily noninvasive cells is consistent with decreased cell-substrate adherence and unrestricted multilayered growth. Thus, it seems that invasiveness is expressed at the cell surface and is related to disturbances in adherence balance rather than in cell proliferation.