Syndecan-2 Is Involved in the Mitogenic Activity and Signaling of Granulocyte-Macrophage Colony-stimulating Factor in Osteoblasts

Modrowski, Dominique; Basle, Michel‐Félix; Lomri, Abderrahim; Marie, Pierre J.

doi:10.1074/jbc.275.13.9178

Cited by 63 publications

(48 citation statements)

References 48 publications

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“…SDC2 is a significant upstream regulator of the TGF-ß signaling pathway (6), regulating signaling by acting as a co-receptor for growth factors. SDC2 facilitates signaling by forming a ternary complex with TGF-ß and its signaling receptors, TGFRI and TGFRII (7)(8)(9). This protein plays diverse roles in tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of altered expression of SDC2 and CYR61 in esophageal squamous cell carcinoma

Huang

Di²,

Xu³

et al. 2009

Oncol Rep

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Abstract. The transforming growth factor ß (TGF-ß) signaling pathway plays an important role in growth and development, and is critically involved in the genesis and development of tumors. Syndecan-2 (SDC2) and Cysteine-rich 61 (CYR61) are important genes in this pathway and SDC2 is known to be a significant upstream regulator of TGF-ß signaling. However, the roles of SDC2 and CYR61 in the development of esophageal squamous cell carcinoma (ESCC) remain unclear. In the present study, we investigated the relationship between SDC2 and CYR61 mRNA expression levels and disease prognosis in patients with ESCC. The mRNA expression of SDC2 and CYR61 was detected by quantitative real-time RT-PCR in 77 tissue specimens. Quantitative realtime RT-PCR showed that SDC2 and CYR61 mRNA expression levels were aberrant in ESCC tissue (P<0.01) and that SDC2 mRNA expression was significantly associated with tumor size (P=0.024) in ESCC. CYR61 mRNA expression was significantly associated with regional lymph node metastasis (P=0.034) and tumor size (P=0.03). A positive correlation between SDC2 and CYR61 (r=0.770; P<0.001) mRNA expression was observed. Moreover, we observed significant associations between altered expression of SDC2/CYR61 and regional lymph node metastasis (P=0.009) and TNM stages (P=0.033). Aberrant mRNA expression of CYR61 and SDC2/CYR61 (P=0.005 and P=0.026, respectively) were significantly associated with patient survival time. The multivariate Cox regression analysis showed that SDC2 and CYR61 were independent prognostic factors for survival. Our findings suggest that SDC2 may act as an a upstream regulator of the TGF-ß signaling pathway and regulate the expression of downstream target genes. Moreover, SDC2 and CYR61 expression affect the severity of cancer, and the survival of patients with ESCC. Importantly, we report that SDC2 and CYR61 are significant, independent prognostic factors for survival in ESCC. These findings may have implications for targeted therapies in patients with ESCC.

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Section: Introductionmentioning

confidence: 99%

Prognostic significance of altered expression of SDC2 and CYR61 in esophageal squamous cell carcinoma

Huang

Di²,

Xu³

et al. 2009

Oncol Rep

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“…Syndecan-2 is involved in regulation of cell adhesions in several cell lines including epithelial cells (20 -22), neuronal cells (23,24), and mesenchymal cells (25). Compared with syndecan-1 and -4, the role of syndecan-2 in cell migration has been less investigated.…”

mentioning

confidence: 99%

“…Compared with syndecan-1 and -4, the role of syndecan-2 in cell migration has been less investigated. However, several reports indicate that syndecan-2 may positively regulate cell migration, since syndecan-2 is normally highly expressed in cells under migratory conditions (22,24,25). In particular, in Lewis lung carcinoma-derived P29 cells, syndecan-2 plays a major role in the interaction with fibronectin and regulates actin stress fiber formation in cooperation with integrin ␣ 5 ␤ 1 (22).…”

mentioning

confidence: 99%

Syndecan-2 Mediates Adhesion and Proliferation of Colon Carcinoma Cells

Park¹,

Kim²,

Lim³

et al. 2002

Journal of Biological Chemistry

155

130

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Syndecan-2 is a transmembrane heparan sulfate proteoglycan whose function at the cell surface is unclear. In this study, we examined the function of syndecan-2 in colon cancer cell lines. In several colon cancer cell lines, syndecan-2 was highly expressed compared with normal cell lines. In contrast, syndecan-1 and -4 were decreased. Cell biological studies using the extracellular domain of recombinant syndecan-2 (2E) or spreading assay with syndecan-2 antibody-coated plates showed that syndecan-2 mediated adhesion and cytoskeletal organization of colon cancer cells. This interaction was critical for the proliferation of colon carcinoma cells. Blocking with 2E or antisense syndecan-2 cDNA induced G 0 /G 1 cell cycle arrest with concomitantly increased expression of p21, p27, and p53. Furthermore, blocking of syndecan-2 through antisense syndecan-2 cDNA significantly reduced tumorigenic activity in colon carcinoma cells. Therefore, increased syndecan-2 expression appears to be a critical for colon carcinoma cell behavior, and syndecan-2 regulates tumorigenic activity through regulation of adhesion and proliferation in colon carcinoma cells.

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“…It has been suggested that syndecan-4 regulates protein levels of the endothelial growth factor receptor (erb-B2 and -B3) in a colon cancer cell line (40). Functional interactions between syndecan-2 and GM-CSF in osteoblasts have been suggested; perhaps syndecan-2 also plays a role as a co-receptor for this cytokine (41). Moreover, syndecan-2 can bind and regulate the signaling of tumor growth factor-ß, and the binding is through the ectodomain of the core protein, with the heparan sulfate chains having only a minor role.…”

Section: Syndecans and Growth Factor Signalingmentioning

confidence: 99%

<a name="home"></a>Specific structural features of syndecans and heparan sulfate chains are needed for cell signaling

Lopes

Dietrich

Nader

2006

Braz J Med Biol Res

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The syndecans, heparan sulfate proteoglycans, are abundant molecules associated with the cell surface and extracellular matrix and consist of a protein core to which heparan sulfate chains are covalently attached. Each of the syndecan core proteins has a short cytoplasmic domain that binds cytosolic regulatory factors. The syndecans also contain highly conserved transmembrane domains and extracellular domains for which important activities are becoming known. These protein domains locate the syndecan on cell surface sites during development and tumor formation where they interact with other receptors to regulate signaling and cytoskeletal organization. The functions of cell surface heparan sulfate proteoglycan have been centered on the role of heparan sulfate chains, located on the outer side of the cell surface, in the binding of a wide array of ligands, including extracellular matrix proteins and soluble growth factors. More recently, the core proteins of the syndecan family transmembrane proteoglycans have also been shown to be involved in cell signaling through interaction with integrins and tyrosine kinase receptors.

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Syndecan-2 Is Involved in the Mitogenic Activity and Signaling of Granulocyte-Macrophage Colony-stimulating Factor in Osteoblasts

Cited by 63 publications

References 48 publications

Prognostic significance of altered expression of SDC2 and CYR61 in esophageal squamous cell carcinoma

Prognostic significance of altered expression of SDC2 and CYR61 in esophageal squamous cell carcinoma

Syndecan-2 Mediates Adhesion and Proliferation of Colon Carcinoma Cells

<a name="home"></a>Specific structural features of syndecans and heparan sulfate chains are needed for cell signaling

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