Abstract 1475: Role of FcγRIIB in metastatic melanoma and rhabdomyosarcoma

Abstract FcγRIIB, known as immunoglobulin gamma Fc region receptor II-b, is a low affinity surface receptor protein for IgG in hematopoietic cells. As an inhibitory receptor, FcγRIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) in their cytoplasmic tails that transduces an inhibitory signal on coligation with the activating receptors. FcγRIIIb is anchored to the plasma membrane via a C-terminus-linked GPI moiety. Present exclusively on human neutrophils, it plays a predominant role in binding of immune complexes. Its co-aggregation with FcγRIIa activates phagocytosis, degranulation, and the respiratory burst leading to destruction of opsonized pathogens. Activation of neutrophils leads to secretion of a proteolytically cleaved soluble form of the receptor corresponding to its two extracellular domains. Soluble Fc RIIIb exerts regulatory functions by competitive inhibition of Fcγ R-dependent effector functions and via binding to the complement receptor CR3. Dysregulation of FcγRIIB can promote the susceptibility and severity of several organ-specific and systemic autoimmune diseases invivo. Studies have recently shown that FcγRIIb increased constitutively in malignant lymphocytes and upregulated ectopically melanoma. Using cDNA microarray analysis, we have found that FcγRIIb is upregulated in metastatic melanoma and rhabdomyosarcoma (RMS). These results suggest that FcγRIIb maybe involved in regulation of progression to metastatic state in tumor.To study the role of FcγRIIb in metastatic diseases; we established model systems which stably express wild-type and mutants FcγRIIb in melanoma B16 and RMS772 cells. Cell colonies stably expressing FcγRIIb were selected and tested in vitro and in vivo. Our data showed that expression of FcγRIIb inhibited cell proliferation and caused a noticeable change in cell morphology, but did not affect cell motility and invasiveness. However, overexpression of FcγRIIb significantly stimulated lung metastasis of both melanoma and RMS cell lines. Our data suggest that over-expression of FcγRIIb promotes metastasis in melanoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1475. doi:10.1158/1538-7445.AM2011-1475