Abstract 4219: miR-34a, miR-93 and miR-200c - novel molecular regulators of osteosarcoma dormancy

There is an increasing interest in elucidating the mechanisms of the earlier stages in tumor progression, the point at which a dormant tumor acquires the ability to grow and metastasize. Although the tumor dormancy phenomenon has important implications for early detection and treatment of cancer, its biology and genetic characteristics are poorly understood. MicroRNAs (miRs), small non-coding RNA molecules which regulate gene expression at the post-transcriptional level, are emerging as key regulators in physiological and pathological processes, including tumorigenesis. We hypothesized that specific miRs may also play a key role in the regulation of tumor dormancy and the “angiogenic switch”. We therefore established a pair of cell lines that generate dormant avascular or fast-growing angiogenic osteosarcomas in SCID mice (Saos-2-D and Saos-2-E respectively). Although these cells share similar growth rate in vitro, when inoculated into mice, Saos-2-E cells generate vascularized and palpable tumors within one month, while Saos-2-D cells remain avascular and non-palpable for a year. Following our hypothesis, miR arrays of Saos-2-D and Saos-2-E cells were performed. Several miRs that were differentially-expressed in the dormant versus fast-growing-tumor-generating cells were selected for further evaluation. Out of those miRs, miR-34a, miR-93 and miR-200c, when administered complexed with a polymeric nanocarrier, reverted several tumor cell lines forming fast-growing tumors to a dormant non-angiogenic phenotype, both in vitro and in vivo. We therefore propose that these three miRs play a role in the switch from dormancy to progressive disease in human osteosarcoma tumors. Uncovering new molecular targets involved in the tumor dormancy phenomenon could provide important tools for novel dormancy-directed tumor therapy strategies. Citation Format: Galia Tiram, Shiran Ferber, Paula Ofek, Noam Shomron, Taturo Udagawa, Sarit Aviel-Ronen, Iris Barshack, Ronit Satchi-Fainaro. miR-34a, miR-93 and miR-200c - novel molecular regulators of osteosarcoma dormancy. [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 4219. doi:10.1158/1538-7445.AM2014-4219