A vital driver for progress in maturing candidates into therapeutic targets of invasive glioma cells will be the skill to validate the biologic results applying mid and high throughput assays of glioma dispersion. This review is supported by grants NS42262 and CA085139. IN 20. Focusing on RAC GUANINE NUCLEOTIDE EXCHANGE Elements TO INHIBIT GLIOMA INVASION B. Salhia,1 N. Tran,2 M. Nakada,2 A. Chan,three M. Berens,1 J. T. Rutka,1 and M. Symons3, 1The Arthur and Sonia Labatt Brain Tumour Study Center, The Hospital for Sick Youngsters, The University of Toronto, Toronto, Ontario, Canada, 2Cancer and Cell Biology Division, The Translational Genomics Investigate Institute, Phoenix, AZ, USA, and three Center for Oncology and Cell Biology, The Feinstein Institute for Healthcare Analysis at North Shore LIJ, Manhasset, NY, USA The invasion of tumor cells into regions of normal brain tissue limits existing therapies for malignant astrocytoma.
We just lately demonstrated a vital role of Rac1, a member within the Rho relatives of minor GTPases, in gli oma invasion. Rho GTPases are activated by guanine nucleotide selleck chemicals exchange factors. There are actually 26 regarded Rac GEFs in the human genome. To determine Rac GEFs that contribute to glioma invasion, we mined microar ray information obtained from 111 human malignant astrocytoma selleck inhibitor specimens and 24 nonneoplastic brain specimens. 3 Rac GEFs, Ect2, Trio, and Vav3, displayed consistent association with substantial grade tumors and poor survival, whereas the expression amounts of Rac1 were very similar across the panel exam ined. We performed quantitative PCR to validate the expression of those Rac GEFs in independent clinical specimens. An immunohistochemical analysis of Rac GEF expression in human brain specimens is in progress.
Using the two radial migration and ex vivo brain slice invasion assays, we also showed that the siRNA mediated depletion of Ect2, Trio, or Vav3 in glioblastoma cell lines considerably inhibited their invasive properties. The depletion of any GEF caused no significant alterations in glioblastoma cell proliferation.
We hypothesize that the respective Rac GEFs mediate the activation of Rac by specific receptors. In summary, our results suggest that Rac GEFs may be a novel target inside the treatment of astrocytoma. IN 21. TENASCIN C STIMULATED GLIOMA CELL INVASION, Position OF BRAIN MICROENVIRONMENT AND MECHANISMS Susobhan Sarkar,1 Robert K. Nuttall,two Shuhong Liu,1 Dylan R. Edwards,two and V. Wee Yong1, 3, Departments of 1Oncology and 3Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada, 2School of Biological Sciences, University of East Anglia, Norwich, Norfolk, United Kingdom The capability of glioma cells to extensively invade the central nervous system is a major cause of the substantial morbidity of primary malignant brain tumors.