Abstract A45: An in vivo examination of the effects of ARID3B on ovarian cancer metastasis in nude mice

Abstract

In 2011, 21,880 women were diagnosed with ovarian cancer and more than 13,850 died from the disease. Unfortunately, the prognosis for most women diagnosed with ovarian cancer is poor due to most patients being diagnosed with local and distant metastases. ARID3B, a DNA binding protein from the AT-rich interactive domain (ARID) family, is overexpressed in late stage neuroblastoma and ovarian cancer. In early development, ARID3B is essential as evidenced by the deaths of Arid3B null embryos by midgestation. The importance of ARID3B in early development and its overexpression in cancer suggest a potential role in cancer progression and metastasis. In addition, our laboratory identified two isoforms of ARID3B a full length (FL) and a short form (SH) that is missing the c-terminal exons 5-9. To determine the effects of the two ARID3B isoforms on metastasis in vivo, human ovarian cancer SKOV3IP cells (selected for their ability to metastasize) overexpressing red fluorescent protein (RFP), ARID3B-FL, or ARID3B-Sh were injected intraperitoneally into nude mice. The mice underwent live optical fluorescence imaging using the Multispectral FX (Kodak) imaging system at frequent intervals to assess tumor burden. The mice were sacrificed when they began to show signs of significant illness. Live imaging of the mice demonstrated that ARID3B-FL expressing SKOV3IP cells formed more and larger tumors more quickly than either SKOV3IP-RFP cells or SKOV3-ARID3B-Sh cells. After sacrificing the mice, tumors and organs were recovered from the abdomen and were imaged ex vivo for tumor burden. Tumors were separated from the organs, weighed, and imaged. The average weights of the tumors were 1.91g for SKOV3IP-RFP derived tumors, 3.22g for SKOV3IP ARID3B-Sh tumors, and 5.46g for SKOV3IP-FL derived tumors. The average tumor burden was greatest for the mice bearing SKOV3IP ARID3B-FL tumors. Gross examination of the tumors post-mortem and post fixation suggested that the tumors from the RFP and ARID3B-Sh expressing cell lines were less vascular or had less vascular leakage than those from the ARID3B-FL mice. Survival analysis showed that the median survival for SKOV3IP ARID3B-FL tumor bearing mice was significantly lower than mice bearing RFP or the ARID3B-Sh expressing tumors (RFP=51 days, ARID3B-Sh=52 days, ARID3B-FL=36 days; P=0.0074). Currently, our lab is addressing potential mechanisms for how ARID3B functions in metastasis. The data presented here suggest that ARID3B plays a significant role in peritoneal metastasis in ovarian cancer. Citation Format: Lynn Roy, Serene Samyesudhas, Martin Carrasco III, Karen Cowden Dahl. An in vivo examination of the effects of ARID3B on ovarian cancer metastasis in nude mice. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A45.