Abstract 933: Bcl-xL overexpression promotes tumor aggressiveness

Abstract

Abstract Bcl-xL is an antiapoptotic protein highly expressed in cancer and contributes to tumor initiation and progression by promoting cell survival. It also promotes tumor angiogenesis and metastasis. By using M14 melanoma and ADF glioblastoma cell lines and their derivative bcl-xL overexpressing clones, in the current study, we investigated the role of bcl-xL in aggressive features of melanoma and glioblastoma models. We found that in both models, bcl-xL overexpression increased in vitro cell migration and invasion and facilitated tumor cells to form de novo vasculogenic structures. Furthermore, bcl-xL overexpressing cells exhibited significantly higher tumorsphere formation capacity, reflecting the self-renewal activity, and expressed high levels of some stem cell markers, supporting the concept that bcl-xL plays essential roles in the maintenance of cancer stem cells phenotype. Forced expression of bcl-xL in melanoma cells also increased vascular endothelial growth factor (VEGF) and matrix metalloprotease-2 (MMP-2) expression, and the activation of hypoxia-inducible factor 1 (HIF-1), a key pathway involved in melanoma vascularization and aggressiveness. On the contrary, no differences were observed after bcl-xL overexpression in glioblastoma model, in terms of HIF-1 expression and activity, and VEGF protein secretion. Immunohistochemical analysis revealed that the expression of the vascular markers, and the vasculogenic mimicry were upregulated in the bcl-xL overexpressing xenografts derived from both tumor histotypes. The work presented here brings further support to the understanding of the malignant actions of bcl-xL both in melanoma and glioblastoma, and in particular to the concept that bcl-xL contributes to the aggressiveness of these two tumor histotypes by promoting invasion, migration, vasculogenic mimicry and cancer stem cells phenotype. It also indicates a cell type-specific effect of bcl-xL on HIF-1/VEGF axis. Citation Format: Maria Grazia Tupone, Daniela Trisciuoglio, Marianna Desideri, Marta Di Martile, Chiara Gabellini, Simonetta Buglioni, Laura De Salvo, Gabriele Alessandrini, Simona D'Aguanno, Donatella Del Bufalo. Bcl-xL overexpression promotes tumor aggressiveness [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 933. doi:10.1158/1538-7445.AM2017-933