In the course of the lab’s investigations, an inverse relationship between glioma cell migration and proliferation has been observed. This study has led to a paradigm of the reciprocal link between invasion and growth of malignant brain tumors. These studies have demonstrated this temporal dichotomy at the phenotypic and gene expression level, arguing that highly invasive glioma cells have a reduced tendency to proliferate; conversely, arrest of migration shifts cells to a more accelerated cell cycle. The empiric reciprocal relationship between migration and proliferation is consistent with the clinical presentation of the most malignant form of brain cancer, glioblastoma multiforme, which often presents as a multifocal disease. Tumor cells, during their trajectory away from the original mass, have reduced commitment to grow, but once these cells have relocated, they resume a proliferative lethal legacy.

The Berens lab has also demonstrated an inverse relationship between glioma cell migration and vulnerability to undergo programmed cell death or apoptosis. The implication of this paradigm is that therapeutic efforts to manage glial tumors require addressing at least two populations of cells: the stationary cells at the tumor core, and the invading cells at the tumor margin. Laser capture microdissection of glioma biopsy specimens is done to collect RNA from cells residing in these two different environments, showing different behaviors. Gene expression analysis demonstrates remarkably different profiles of cellular pathways between these two populations; these pathways control cell motility, proliferation, and various mediators in the cell survival / apoptosis pathways.

In collaboration with an interdisciplinary team, the group is studying changes in glioma gene expression that accompany the transition of cell egress from multicellular spheroids, the adoption of an invasive/migratory phenotype, and the subsequent cessation of invasion that coincides with resumed proliferation. These experiments are designed to discover key genetic regulation of the cancer cell transition from proliferative to migratory behaviors. The findings may indicate strategies by which to control the spread and metastasis of cancer.

The translational applications of our studies include the discovery and validation of markers of glioma invasion, which may have value in diagnostic or prognostic routines. From a treatment perspective, the lab has developed and employed screening technologies by which to test libraries of small, nontoxic molecules for their migration-arresting properties. Active candidate compounds are being tested for synergistic effects with conventional chemotherapeutic agents or with radiation therapy. Preliminary preclinical in vivo experiments support the potentiation of cytotoxic therapy when tumors are treated with migration arresting compounds.

Dr. Berens obtained his undergraduate degree in zoology from Arizona State University. His doctoral work was completed at University of Arizona in the field of cancer biology. He is currently the Senior Investigator at the Brain Tumor Research Unit.