Abstract 3255: The role of Hdj2 protein in metastatic progression of experimental intracranial glioma

Abstract

Abstract Glioblastoma is one of the most malignant cancer types with median survival of 15 months regardless of the application of combined radio- and chemotherapy. Expression of Hdj2 negatively correlates with the increase of tumor aggressiveness. For assessment of Hdj2 role in tumor progression, invasiveness and metastasis formation in gliomas we developed three C6-based cell lines with Hdj2 and related proteins knock-down: C6 shHsp70, C6 shHdj1 and C6 shHdj2 itself. Following intracranial injection of the modified tumor cells the animals’ survival was estimated. As compared to control C6 (25.4±3.9 days) and C6 shHdj1 (25.5±3.8) we observed a nearly 1.5-fold decrease in survival in C6 shHdj2 (16.8±3.5 days) (P<0.05). On the contrary, in C6 shHsp70 group the survival increased up to 42.5±12.0 days (the increase is completely explainable by the slower growth rate of the culture). Subsequent MR imaging and histological analysis of the tumors demonstrated elevated invasiveness and metastatic activity in C6 shHdj2 group in comparison to C6 shHsp70, C6 shHdj1 and control C6. High migration activity and the ability of detached C6 shHdj2 cells to settle on the substrate was proved in wound-healing assay, colony forming assay and calcium-dependent cell aggregation assay. Immunofluorescence analyses showed loss of membrane-expressed N-cadherin and loss of intercellular contacts mediated by N-cadherin in C6 shHdj2 cells in comparison to other considered cell lines. Actin staining with rhodamine-falloidin revealed highly abundant leading edges in C6 shHdj2 culture. Decrease of Hdj2 expression in gliomas has proved to be of high importance in tumor progression and formation of metastasis. Citation Format: Darya A. Meshalkina, Maxim A. Shevtsov, Boris A. Margulis, Irina V. Guzhova. The role of Hdj2 protein in metastatic progression of experimental intracranial glioma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3255. doi:10.1158/1538-7445.AM2015-3255