Testing the “Go or Grow” Hypothesis in Human Medulloblastoma Cell Lines in Two and Three Dimensions

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Abstract

OBJECTIVE The “Go or Grow” hypothesis proposes that cell division and cell migration are temporally exclusive events and that tumor cells defer cell division to migrate. The purpose of this study was to assess the Go or Grow hypothesis using medulloblastoma cell lines in directional migration and invasion assays in monolayer and three-dimensional cultures. METHODS Time-lapse videomicroscopy was used to continually monitor the directional migration, invasion, and mitosis of individual cells. The mitotic activity observed by time-lapse videomicroscopy was compared with staining for the proliferating cell nuclear antigen Ki-67. RESULTS A positive correlation exists between the migratory/invasive and mitotic activities of the four medulloblastoma cell lines studied. Within individual cell lines, however, migration and invasion distances are not influenced by the number of cell divisions. Time-lapse videomicroscopy and Ki-67 staining revealed similar trends in mitotic activity between migrating and nonmigrating cells within cell lines. Analysis of cell velocities before, after, and between cell divisions revealed an increase in cell velocity after cell divisions. CONCLUSION In the models studied, four medulloblastoma cell lines do not defer cell proliferation for migration across an uncoated surface or invasion of a Type I collagen matrix, contrary to the Go or Grow hypothesis. Migrating and invading cells continue to proliferate and migrate/invade a cell line-dependent distance irrespective of the number of divisions that take place. These findings emphasize the need to evaluate the effect of future therapies on both biological events and, if possible, to identify intracellular signaling proteins that negatively regulate medulloblastoma migration/invasion and proliferation.

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