Abstract Neuroblastoma (NB) is the most common extracranial pediatric cancer, accounting for 15% of all childhood cancer deaths. Recently, our lab reported the novel finding of ICAM-2 expression in NB cell lines and primary NB tumor cells. Interestingly, ICAM-2-expressing NB cells exhibited decreased motility in vitro and decreased metastatic potential in vivo. In these ICAM-2-expressing non-metastatic NB cells, the cytoplasmic domain of ICAM-2 interacted with β-actinin, which in turn interacted with actin, leading to subsequent redistribution of actin fibers to a non-motile state. The goal of the current study is determining the potential role of the ICAM-2 extracellular domain in NB metastasis development. Therefore, we constructed a series of chimeric fusion proteins, one of which consists of the extra cellular domain of CD89 with the transmembrane and cytoplasmic domains of ICAM-2 (CD89αED). CD89 is the receptor for IgA, and bears striking similarity to ICAM-2 in terms of size (287AA vs. 275AA, respectively) and structure. Both are immunoglobulin superfamily members with two Ig-like domains, six extracellular N-glycosylation sites, and short cytoplasmic domains. Furthermore, there is no literature implicating CD89 in cancer progression. This construct was stably transfected into a non-ICAM-2 expressing SK-N-AS NB cell line, and protein expression was confirmed by flow cytometry and western blot. Our preliminary data showed distinct phenotypic differences between NB cells stably transfected with the CD89αED construct compared to wild type ICAM-2. In scratch assays, CD89αED cells showed faster migration ability than ICAM-2 wt (75% vs. 50% wound closure) at 72 hour time points. Furthermore, in anchorage-independent colony growth in soft agar, CD89αED cells formed a significantly (P < 0.001) higher number of colonies compared to ICAM-2 wt. Ongoing work focuses on determining the effect of CD89αED on F-actin modification and regulation of potential downstream signaling pathways. This work was supported by the UAB Comprehensive Cancer Center Young Supporters Board - New Faculty Development Award 2010 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2504. doi:1538-7445.AM2012-2504