Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
Department of Dermatology, Kyoto University Hospital, Kyoto, Japan.
Exp Dermatol. 2018 Jun;27(6):641-646. doi: 10.1111/exd.13523.
The signalling lymphocytic activation molecule family member 8 (SLAMF8)/CD353 is a member of the CD2 family of proteins. Its ligand has not been identified. SLAMF8 is expressed by macrophages and suppresses cellular functions. No study has yet explored SLAMF8 expression or function in human mastocytosis, which features oncogenic KIT-mediated proliferation of human mast cells. SLAMF8 protein was expressed in human mastocytosis cells, immunohistochemically. SLAMF8 expression was also evident in the human mast cell lines, HMC1.2 (expressing oncogenic KIT) and LAD2 (expressing wild-type KIT) cells. SLAMF8 knock-down significantly reduced the KIT-mediated growth of HMC1.2 cells but not that of LAD2 cells. SLAMF8 knock-down HMC1.2 cells exhibited significant attenuation of SHP-2 activation and oncogenic KIT-mediated RAS-RAF-ERK signalling. An interaction between SLAMF8 and SHP-2 was confirmed in HMC1.2 cells and all pathological mastocytosis specimens examined (19 of 19 cases, 100%). Thus, SLAMF8 is involved in oncogenic KIT-mediated RAS-RAF-ERK signalling and the subsequent growth of human neoplastic mast cells mediated by SHP-2. SLAMF8 is a possible therapeutic target in human mastocytosis patients.
信号淋巴细胞激活分子家族成员 8（SLAMF8）/CD353 是 CD2 蛋白家族的成员。其配体尚未确定。SLAMF8 由巨噬细胞表达，并抑制细胞功能。目前尚无研究探讨 SLAMF8 在人肥大细胞中的表达或功能，而人肥大细胞的特征是致癌性 KIT 介导的人肥大细胞增殖。SLAMF8 蛋白在人肥大细胞肿瘤细胞中通过免疫组织化学表达。SLAMF8 表达也在人肥大细胞瘤系 HMC1.2（表达致癌性 KIT）和 LAD2（表达野生型 KIT）细胞中明显。SLAMF8 敲低显著降低了 HMC1.2 细胞中 KIT 介导的生长，但对 LAD2 细胞没有影响。SLAMF8 敲低的 HMC1.2 细胞显示 SHP-2 激活和致癌性 KIT 介导的 RAS-RAF-ERK 信号的显著衰减。在 HMC1.2 细胞和所有检查的病理性肥大细胞标本（19 例中的 19 例，100%）中均证实了 SLAMF8 与 SHP-2 之间的相互作用。因此，SLAMF8 参与了致癌性 KIT 介导的 RAS-RAF-ERK 信号和随后由 SHP-2 介导的人类肿瘤性肥大细胞的生长。SLAMF8 可能是人类肥大细胞患者的治疗靶点。
