RELATE WITH Poor PATIENT End result Nhan L. IN 22. CXCR4 EXPRESSION Like 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 Medical Center, Nashville, TN, USA The prognosis of patients with malignant gliomas stays dismal. The clinical aggressiveness and remedy refractory nature of those neoplasms is derived, in big aspect, from their very proliferative and infiltrative nature. As this kind of, the improvement of an efficient therapeutic modality for these tumors will call for a much better knowing in the certain biologic cues that drive glioma growth and invasiveness. We determined regardless of whether the in vitro and in vivo association of the cell surface chemokine receptor, CXCR4, was connected to histologic grade and the advancement of an invasive phenotype in glioma.
Utilizing absolutely quantitative genuine time PCR, we analyzed the expression levels of CXCR4 and its corresponding ligand CXCL12 in 90 special patient derived glioma tissue samples. The expression of CXCR4 and CXCL12 was further verified on the protein level applying selleck inhibitor immunohistochemi cal evaluation. We then determined the functional part of CXCR4 in glioma by assessing the contribution of this receptor to tumor cell invasiveness. Making use of an experimental rodent model of intracranial selleck chemical BAY 11-7082 glioma, we isolated infiltra tive glioma cells by means of laser capture microdissection and when once again analyzed CXCR4 expression ranges making use of quantitative real time PCR. Sub sequently, glioma cells have been handled with CXCR4 neutralization antibody or compact interference RNA technology, and their infiltrative capabilities have been characterized by an in vitro matrigel invasion assay.
We demonstrated that CXCR4 expression correlated strongly with escalating tumor grade in World Health Organization grade II by way of IV gliomas and identified a significant association in between CXCR4 and CXCL12 expres sion ranges inside a provided grade of tumor. Furthermore, we uncovered considerably 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 between 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 as being a potential therapeutic target for the treatment method of malignant glioma. IN 23. INCREASED FN14 EXPRESSION Amounts PROMOTE GLIOMA CELL INVASION VIA RAC1 AND NF KB AND COR