Syntenin is an adaptor molecule containing 2 PDZ domains which mediate molecular interactions with diverse integral or cytoplasmic proteins. Most of the results on the biological function of syntenin were obtained from studies with malignant cells, necessitating exploration into the role of syntenin in normal cells. To understand its role in normal cells, we investigated expression and function of syntenin in human lymphoid tissue and cells in situ and in vitro. Syntenin expression was denser in the germinal center than in the extrafollicular area. Inside the germinal center, syntenin expression was obvious in follicular dendritic cells (FDCs). Flow cytometric analysis with isolated cells confirmed a weak expression of syntenin in T and B cells and a strong expression in FDCs. In FDC-like cells, HK cells, most syntenin proteins were found in the cytoplasm compared to weak expression in the nucleus. To study the function of syntenin in FDC, we examined its role in the focal adhesion of HK cells by depleting syntenin by siRNA technology. Knockdown of syntenin markedly impaired focal adhesion kinase phosphorylation in HK cells. These results suggest that syntenin may play an important role in normal physiology as well as in cancer pathology.
B-Lymphocytes ; Cytoplasm ; Dendritic Cells, Follicular* ; Focal Adhesion Protein-Tyrosine Kinases* ; Focal Adhesions* ; Germinal Center ; Humans* ; Lymphoid Tissue ; PDZ Domains ; Phosphorylation ; Proteins ; RNA, Small Interfering ; Syntenins*

Syntenin is overexpressed in multiple human cancers and is newly recognized as a novel regulator in melanoma metastasis. It functions as a scaffolding protein, via its two PDZ domains interacting with multiple transmembrane and cytoplasmic partners to regulate many of the major signaling pathways involved in various cellular processes, such as cell surface receptor clustering, protein trafficking, cytoskeleton remodeling, and activation of transcription factor, and results in the increased abilities for tumor cell growth, adhesion, angiogenesis, invasion and metastasis. The present article attempts to review the structure and functions of syntenin by summarizing our current knowledge on the interacting partners and diverse signaling pathways related to syntenin, and highlight the importance of syntenin as a new potential therapeutic target for the aggressive human melanoma.
Animals ; Biomarkers, Tumor ; genetics ; metabolism ; Humans ; Melanoma ; genetics ; metabolism ; pathology ; Neoplasm Metastasis ; PDZ Domains ; genetics ; Signal Transduction ; Syntenins ; chemistry ; genetics ; metabolism

OBJECTIVETo analyze the clinical significance of syndecan binding protein (SDCBP) expression in human colorectal carcinoma (CRC) and its value in predicting the postoperative survival of the patients.

METHODSThe follow-up data for 10 years were collected from 109 primary CRC patients with immunohistochemical data of SDCBP expression in the tumor tissues. The relationship between SDCBP expression and the clinical factors was analyzed, and survival analysis was performed using the Kaplan-Meier and Cox regression analysis models.

RESULTSSDCBP expression in CRC was significantly associated with the postoperative survival time (χ(2)=8.336, P=0.004) and lymph node metastasis (P=0.001) of the patients, but not with age, gender, depth of invasion, tissue differentiation or histological type of the tumor. Kaplan-Meier survival curves showed that the patients expression high levels of SDCBP in the CRC tissues had a significantly shorter postoperative mean survival time and a lower 7-year survival rate than those with low SDCBP expressions [52.300∓6.508 vs 86.184∓5.358 months, (38.6∓6.4)% vs (61.5∓6.7)%; χ(2)=10.585, P=0.001]. Multivariate Cox analysis revealed that a high expression of SDCBP (B=0.605, P=0.034) and lymph node metastasis (B=0.677, P=0.013) were the main factors related to death in CRC patients.

CONCLUSIONSDCBP expression level can serve as an indicator for lymph node metastasis, TNM staging, and outcome prediction of CRC.

Biomarkers, Tumor ; Colorectal Neoplasms ; diagnosis ; metabolism ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Multivariate Analysis ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Survival Rate ; Syntenins ; metabolism

PURPOSE: Echinacea, a traditional plant medicine has been used as immune-stimulant. Recent studies have revealed that extract of Echinacea has immunostimulatory effects on human blood mononuclear cells. This study was designed for the purpose of screening the genes associated with immunologic effects of Echinacea on monocytes and dendritic cells using a cDNA microarray chip. METHODS: CD14+monocyte cells were cultured for one day with Echinacea extract (final concentration: 50 microgram/mL) in experiment 1, but were cultured without Echinacea in experiment 2. The gene expression of these cultured monocytes was analyzed using the cDNA microarray chip. Dendritic cells produced from CD14+monocyte were cultured for five days with GM-CSF and IL-4, and then cultured for one day with Echinacea in experiment 3, but were done without Echinacea in experiment 4. RESULTS: In experiments 1 and 2, there were 17 significantly expressed genes with average expression ratios above 2.5, including interferon gamma-inducible protein 30 (IFI 30), CDC (cell-division-cylcle)-like kinase 2 (CLK 2), syndecan binding protein (syntenin), superoxide dismutase 2, etc. In experiments 3 and 4, there were 24 gene, with significantly expressed genes were 24 genes, which were insulin-like growth factor 2 (somatomedin A), methyl-CpG binding domain protein 3, IFI 30, small inducible cytokine subfamily A, member 22, etc. The genes encoding CD44, IFI 30, mannose receptor C type 1 (MRC 1), chemokine receptor 7 (CCR 7), CLK 2, syntenin and cytochrome C oxidase subunit VIII were significantly expressed in both monocytes and dendritic cells cultured with Echinacea. CONCLUSION: This study employed a cDNA microarray chip to elicit the immune-associated gene profile; the expression was enhanced by Echinacea in CD14+monocytes and dendritic cells. Thus we laid the basis for the quantitative and functional analysis of genes induced by Echinacea in monocytes and monocyte-derived dendritic cells.
Carrier Proteins ; Centers for Disease Control and Prevention (U.S.) ; Dendritic Cells* ; Echinacea* ; Electron Transport Complex IV ; Gene Expression* ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Interferons ; Interleukin-4 ; Mannose ; Mass Screening ; Monocytes* ; Oligonucleotide Array Sequence Analysis ; Phosphotransferases ; Plants ; Superoxide Dismutase ; Syndecans ; Syntenins

Syntenin is a PDZ domain-containing adaptor protein that has been recently shown to regulate migration and invasion in several tumors. Small cell lung cancer (SCLC) is notorious for its invasiveness and strong potential for metastasis. We therefore studied the influence of syntenin on the invasiveness of SCLC. Immunohistochemistry in tumor tissues showed that syntenin was more frequently expressed in small cell carcinomas than other neuroendocrine tumors, such as carcinoids and neuroblastomas, suggesting that syntenin expression may be related to more aggressive forms of neuroendocrine tumors. In SCLC patients, syntenin overexpression in tumor cells was significantly associated with more extensive and advanced disease at the time of diagnosis (P=0.029). Overexpression of syntenin in SCLC cells that were intrinsically syntenin-low increased the invasiveness of cells and led to the induction of extracellular matrix (ECM)-degrading membrane type 1-matrix metalloproteinase (MT1-MMP) and matrix metalloproteinase 2 (MMP2). In contrast, suppression of syntenin in syntenin-high cells was associated with the downregulation of MT1-MMP. Contrary to the results of previous studies using malignant melanomas and breast carcinomas, signaling cascades were shown to be further transduced through p38 MAPK and PI3K/AKT, with activation of SP1 rather than NF-kappaB, under circumstances not involving ECM interaction. In addition, the upstream molecule focal adhesion kinase was induced by syntenin activation, in spite of the absence of ECM interaction. These results suggest that syntenin might contribute to the invasiveness of SCLC and could be utilized as a new therapeutic target for controlling invasion and metastasis in SCLC.
Cell Line, Tumor ; Focal Adhesion Protein-Tyrosine Kinases/*metabolism ; Humans ; Matrix Metalloproteinase 14/genetics/metabolism ; Matrix Metalloproteinase 2/genetics/metabolism ; Neoplasm Invasiveness ; Phosphatidylinositol 3-Kinases/*metabolism ; Proto-Oncogene Proteins c-akt/*metabolism ; Signal Transduction ; Small Cell Lung Carcinoma/*metabolism/pathology ; Sp1 Transcription Factor/*metabolism ; Syntenins/genetics/*metabolism ; p38 Mitogen-Activated Protein Kinases/*metabolism