Ass1, Anxa4 And Mvp Underlie Acquired Multicellular Resistance Of Mesothelioma 3d Cell Cultures

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Cancer cells are usually studied in flat 2D monolayers however, solid tumors, such as malignant mesothelioma, grow as 3D masses. When tumor cells are grown as 3D structures, they acquire multi-cellular resistance to apoptosis, resembling the stubborn chemoresistance seen in patients. In this study, we have identified a gene expression signature that is specific for 3D spheroids, possibly underlying multicellular resistance. By comparing this signature with the data from two sets of publicly-available gene expression datasets of patients’ specimens we have identified three genes in common, genes that may play a role in multicellular resistance: ASS1, ANXA4 and MVP. Moreover, we have studied the levels of the proteins encoded by the three genes and have begun investigating how their ablation by RNAi influences the response to chemotherapy. Furthemore, by Connectivity Analysis, we have found two safe and patent-free candidate drugs that can reduce the expression levels of the three genes and undermine the acquired chemoresistance of spheroids. Such drugs would have potential as adjuncts to chemotherapy. These studies will not only clarify the role of ASS1, ANXA4 and MVP in mesothelioma and provide therapeutic insights but also advance the use of spheroids as a more realistic model for studying tumor biology. Citation Format: Dario Barbone, Loes van Dam, Shu-Dong Zhang, Jithesh Puthen, Dean Fennell, V. Courtney Broaddus. ASS1, ANXA4 and MVP underlie acquired multicellular resistance of mesothelioma 3D cell cultures. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 696. doi:10.1158/1538-7445.AM2014-696