SLAM family member 8 is expressed in and enhances the growth of anaplastic large cell lymphoma

Abstract

Signaling lymphocytic activation molecule family member 8 (SLAMF8) / B-lymphocyte activator macrophage expressed/CD353 is a member of the CD2 family. SLAMF8 suppresses macrophage function but enhances the growth of neoplastic mast cells via SHP-2. In this study, we found that some anaplastic large cell lymphoma (ALCL) samples were immunohistochemically positive for SLAMF8. However, we found no significant differences between SLAMF8-positive and SLAMF8-negative ALCL samples with respect to age, gender, site, or prognosis. We also identified SLAMF8 expression in ALCL cell lines, Karpas299, and SU-DHL-1. SLAMF8 knockdown decreased the activation of SHP-2 and the growth of these cell lines, and increased the apoptosis of these cell lines. In addition, we observed the interaction between SLAMF8 and SHP-2 in these cell lines using the DuoLink in situ kit. Taken together, these results suggest that SLAMF8 may enhance the growth of ALCL via SHP-2 interaction. The signaling lymphocytic activation molecule (SLAM) family of receptors is expressed by and regulates the functions of immune cells 1,2. SLAM family member 8 (SLAMF8)/B-lymphocyte activator macrophage expressed/ CD353 is a cell-surface protein and a member of the CD2 family 1,2. However, its ligand has not yet been identified. SLAMF8 is a potent marker for tumor infiltrating T cells. SLAMF8 are abundantly expressed in T cells infiltrating in pediatric cancers and Epstein-Barr virus-positive gastric cancers, and thought to be a marker for potential immunotherapy targets 3,4. In addition, SLAMF8 is expressed by and suppresses macrophage the function of human macrophage 5,6. SLAMF8 is also expressed by and enhances the growth of human neoplastic mast cells 7. SLAM family signaling is generally mediated by SLAM-associated protein (SAP) or Ewing's sarcoma-associated transcript 2 (EAT-2) in lymphocytes and macrophage cells 1,2 , although SLAMF8 signaling is mediated by the Src homology region 2 domain-containing phosphatase-2 (SHP-2) in human mast cells 7. To the best of our knowledge, no studies have explored the expression of SLAMF8 in anaplastic large cell lymphoma (ALCL). ALCL cells are typically large, have abundant cytoplasm and horseshoe-shaped nuclei, and are positive for CD30 on the cell membrane and in the Golgi region 8. The expression of anaplastic lymphoma kinase (ALK) is clinically important, and the prognosis of ALK-positive ALCL is favorable compared to ALK-negative ALCL. There are three subtypes of ALCL: ALK-positive, ALK-negative, and primary cutaneous ALCL. In this study, we analyzed the expression and function of SLAMF8 in ALCL clinical samples and cell lines. Results Human ALCLs express SLAMF8 mRNA and protein. We examined the expression of SLAMF8 mRNA and protein in the human ALCL cell lines SU-DHL-1 and Karpas299 using RT-PCR and immunoblotting, respectively. Both cell lines expressed SLAMF8 mRNA and protein (Fig. 1A,B). Both cell lines showed ALK translocation 9,10 and we treated these with an ALK inhibitor, crizotinib 11. The administration of cr...

Identification and Validation of Novel Biomarkers for Hepatocellular Carcinoma, Liver Fibrosis/Cirrhosis and Chronic Hepatitis B via Transcriptome Sequencing Technology

“…SLAMF8/CD353 is a member of the SLAMF receptor family that modulates the activation and functions of many immune cells. 50 , 51 Previous studies indicated that SLAMF8 was a diagnostic and prognostic marker for pulmonary tuberculosis, 31 glioma 23 and anaplastic large cell lymphoma. 51 Zeng et al 25 demonstrated that the combined deficiency of SLAMF8 and SLAMF9 could prevent endotoxin-induced hepatic inflammation, and could act as the promising therapeutic targets for acute liver injury.…”

“… 50 , 51 Previous studies indicated that SLAMF8 was a diagnostic and prognostic marker for pulmonary tuberculosis, 31 glioma 23 and anaplastic large cell lymphoma. 51 Zeng et al 25 demonstrated that the combined deficiency of SLAMF8 and SLAMF9 could prevent endotoxin-induced hepatic inflammation, and could act as the promising therapeutic targets for acute liver injury. However, our findings demonstrated a significant increase in the expression of SLAMF8 in HBV-related liver injuries, and its level increased with the severity of these injuries ( Figures 3 and 4 ).…”

Identification and Validation of Novel Biomarkers for HBV-Associated Hepatocellular Carcinoma, Liver Fibrosis/Cirrhosis and Chronic Hepatitis: A Case Control Study

“…4). SLAMF8/CD353 is a member of the SLAMF receptor family that modulates the activation and functions of many immune cells [31,32].…”

“…4). SLAMF8/CD353 is a member of the SLAMF receptor family that modulates the activation and functions of many immune cells [31,32]. Zeng et al [33] demonstrated that the combined de ciency of SLAMF8 and SLAMF9 could prevent endotoxin-induced hepatic in ammation and might serve as promising therapeutic targets for acute liver injury.…”

Prostaglandins and calprotectin are genetically and functionally linked to the Inflammatory Bowel Diseases

“…This shared effect was also observed in the specific list of genes whose expression was altered in response to these ORFs (S2 Fig) . While more modest, we also observed that the HITS for IBD ORFs ETS2 and ZBTB40 shared a significant GO annotation (immune system process) (S3A, S3B, S4A and S5A Tables). Expressing the ORFs of ETS2 or ZBTB40 in THP-1 cells resulted in up-or down-regulation of a common set of genes (S3 Fig) primarily involved in the recruitment and extravasation of inflammatory cells [20][21][22][23][24]. While much more limited in terms of shared impact on the THP-1 transcriptome, the three shared HITs of SLC39A11 and NOD2 (S4 Fig) all impact on monocyte/macrophage polarization [25][26][27].…”