Abstract 498: Anti-invasive potential of alginate microcapsule encapsulating TIMP 2-engineered cells against malignant glioma cells

Abstract Objectives. 293T was genetically modified to secrete tissue inhibitor of metalloproteinase-2 (TIMP-2) (abbreviated as 293TIMP2 cells) and 293TIMP2 cells were encapsulated into alginate microcapsules to produce TIMP-2 protien continuously. Since TIMP-2 is known to inhibit matrix metalloproteinase-2 (MMP-2) expression of tumor cells, it could be inhibit invasion of tumor cells through extracellular matrix. The anti-invasive potential of the microcapsules was studied in vitro against U87MG glioma cells. Experimental. The TIMP-2 gene was transfected to 293T cells and the genetically engineered 293TIMP2 cells were encapsulted into alginate microcapsules. The released TIMP-2 protein was examined with Western blot analysis and the anti-invasive potential against U86MG glioma cells was tested with gelatin zymography for matrix metalloproteinase-2 (MMP-2) and a Matrigel assay for invasion. Results. Cell viability within the alginate microcapsules was properly maintained at a cell density of 5×106 cell density. Since polycationic polymers are helpful to maintain mechanical strength of microcapsules with good cell viability, alginate microcapsules were reinforced with chitosan (0.1 % wt/vol). Expression of TIMP-2 protein in cell lysate and the secreted TIMP-2 into conditioned media were confirmed with Western blot analysis. Alginate microcapsules encapsulating 293TIMP2 cells properly released TIMP-2 protein into the medium and the released TIMP-2 protein was effective in inhibiting MMP-2 expression and invasion of U87MG glioma cells. Conclusion. These results indicated that alginate microcapsules encapsulating 293TIMP2 cells are superior candidates for anti-invasive therapy of glioma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 498. doi:1538-7445.AM2012-498