Dichotomy of astrocytoma migration and proliferation

Abstract

Astrocytomas often show high rates of local invasion that lead to local recurrence of the disease. Histologically, the most highly invasive astrocytoma cells are detected in isolation rather than as nests of tumor. Our study attempted to determine whether the migratory response to extracellular substrates influences the proliferative behavior of these highly invasive cells. The preferential and specific migratory response of human astrocytoma cells to extracellular matrix proteins was assessed by a microliter scale migration assay. Growth curve studies on protein ligands permissive (merosin) for cell migration indicated that the lag phase was protracted compared with cells seeded on non-permissive proteins (vitronectin). Once a certain cell density was reached, logarithmic proliferation was indistinguishable on the different proteins. The proliferation index of populations of cells migrating on merosin and vitronectin was measured by both BrdU incorporation and MIB-1 immunocytochemistry labeling. Cells seeded on vitronectin showed higher proliferation throughout the population than cells seeded on merosin. On merosin, the more migratory cells at the periphery were less proliferative than non-migratory cells in the central region of that population. The integrin-associated signal transduction protein, p125FAK, was heavily localized in the membrane of non-migrating cells and largely absent in migrating astrocytoma cells. We conclude that temporally, proliferation and migration are mutually exclusive behaviors. Cell density or non-permissive substrates that inhibit cell motility favor a more proliferative phenotype. Conversely, active migration suppresses cell proliferation.