RELATE WITH Poor PATIENT Outcome Nhan L. IN 22. CXCR4 EXPRESSION Being a MARKER FOR TUMOR GRADE AND INVASIVENESS IN MALIGNANT GLIOMA Charles B. Stevenson, Karen K. Deal, Stephanie M. Miller, Juan G. Valadez, Jason A. Winston, Reid C. Thompson, and Moneeb Ehtesham, Division of Neurological Surgical treatment, Vanderbilt University Healthcare Center, Nashville, TN, USA The prognosis of sufferers with malignant gliomas stays dismal. The clinical aggressiveness and treatment method refractory nature of these neoplasms is derived, in large aspect, from their very proliferative and infiltrative nature. As this kind of, the advancement of an effective therapeutic modality for these tumors will require a much better understanding from the exact biologic cues that drive glioma growth and invasiveness. We determined whether the in vitro and in vivo association of the cell surface chemokine receptor, CXCR4, was connected to histologic grade along with the development of an invasive phenotype in glioma.
Employing thoroughly quantitative real time PCR, we analyzed the expression amounts of CXCR4 and its corresponding ligand CXCL12 in 90 unique patient derived glioma tissue samples. The expression of CXCR4 and CXCL12 was even more verified with the protein level using SP600125 immunohistochemi cal analysis. We then established the functional function of CXCR4 in glioma by assessing the contribution of this receptor to tumor cell invasiveness. Working with an experimental rodent model of intracranial kinase inhibitor Nutlin-3 glioma, we isolated infiltra tive glioma cells by means of laser capture microdissection and when once again analyzed CXCR4 expression ranges applying quantitative serious time PCR. Sub sequently, glioma cells were handled with CXCR4 neutralization antibody or smaller interference RNA technological innovation, and their infiltrative abilities have been characterized by an in vitro matrigel invasion assay.
We demonstrated that CXCR4 expression correlated strongly with rising tumor grade in Planet Health Organization grade II by way of IV gliomas and noticed a substantial association amongst CXCR4 and CXCL12 expres sion levels inside a offered grade of tumor. Additionally, we identified substantially elevated expression of CXCR4

in infiltrative glioma cells compared with noninvasive tumor cells. Importantly, abrogation of the CXCR4 function significantly impaired glioma cell invasiveness in matrigel based tumor infil tration assays. Together, these findings demonstrate a strong association involving expression of CXCR4 and histopathologic aggressiveness, as well as assumption of an invasive phenotype in glioma cells. In light of this, these data underscore the importance of CXCR4 being a potential therapeutic target for the treatment method of malignant glioma. IN 23. INCREASED FN14 EXPRESSION Levels PROMOTE GLIOMA CELL INVASION VIA RAC1 AND NF KB AND COR