Participation of Syndecan 2 in the Induction of Stress Fiber Formation in Cooperation with Integrin α5β1: Structural Characteristics of Heparan Sulfate Chains with Avidity to COOH-Terminal Heparin-Binding Domain of Fibronectin

Kusano, Yuri; Oguri, Kayoko; Nagayasu, Yuko; Munesue, Seiichi; Ishihara, Masayuki; Saiki, Ikuo; Yonekura, Hideto; Yamamoto, Hiroshi; Okayama, Minoru

doi:10.1006/excr.2000.4802

Cited by 92 publications

(80 citation statements)

References 48 publications

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“…It has been known that expressions of syndecan-1 and -4 are reduced in colon carcinoma cells compared to adenoma (Jayson et al, 1999), and syndecan-2 may function as an adhesion receptor in Lewis lung carcinoma (Kusano et al, 2000). These reports prompted us to investigate the function of syndecan-2 on the morphology of colon cancer cells.…”

Section: Tsa-induced Morphological Changes Y Kim Et Almentioning

confidence: 99%

Decreased syndecan-2 expression correlates with trichostatin-A induced-morphological changes and reduced tumorigenic activity in colon carcinoma cells

et al. 2003

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The inhibition of histone deacetylase activity is known to induce morphological changes of transformed cells. In this study, we investigated the effect of the specific HDAC inhibitor, trichostatin A (TSA), on colon carcinoma cell lines. Treatment of human colorectal carcinoma cells, KM1214 and KM12SM, with TSA induced distinct morphological changes. Both cell lines, which normally piled up in layers without clear boundary, became more flattened, and formed monolayers with evident boundaries between cells, with concomitant increased actin filament organization. Cell-cell interaction was not affected much, based on expression level, membrane localization, and interaction of E-cadherin with b-catenin. In contrast, syndecan-2 expression was dramatically reduced and it was correlated with the morphological changes of colon carcinoma cells. Consistently, downregulation of syndecan-2 expression by antisense cDNA clearly mimicked the morphological changes in KM12SM and reduced anchorage-independent growth of colon cancer cells. All these results indicate that reduced syndecan-2 expression correlates with TSA-induced morphological changes and reduced tumorigenic activity in colon carcinoma cells.

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Section: Tsa-induced Morphological Changes Y Kim Et Almentioning

confidence: 99%

Decreased syndecan-2 expression correlates with trichostatin-A induced-morphological changes and reduced tumorigenic activity in colon carcinoma cells

et al. 2003

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“…Previous studies have shown that syndecan-1 regulates tumor activity in pancreatic (7), gastric (8), and breast carcinomas (9). Syndecan-1 may thus play multiple roles in tumorigenic activity and perform various tissue-and/or tumor stage-specific functions (10). Syndecan-4 expression is reduced in colon carcinoma cells (11,12) and appears to correlate with increased tumorigenic activity (e.g.…”

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confidence: 99%

Syndecan-2 Regulates the Migratory Potential of Melanoma Cells

Lee

Park

Chung

et al. 2009

Journal of Biological Chemistry

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Syndecan-2, a transmembrane heparan sulfate proteoglycan, is a critical mediator in the tumorigenesis of colon carcinoma cells. We explored the function of syndecan-2 in melanoma, one of the most invasive types of cancers, and found that the expression of this protein was elevated in tissue samples from both nevus and malignant human melanomas but not in melanocytes of the normal human skin tissues. Similarly, elevated syndecan-2 expression was observed in various melanoma cell lines. Overexpression of syndecan-2 enhanced migration and invasion of melanoma cells, whereas the opposite was observed when syndecan-2 levels were knocked down using small inhibitory RNAs. Syndecan-2 expression was enhanced by fibroblast growth factor-2, which is known to stimulate melanoma cell migration; however, ␣-melanocyte-stimulating hormone decreased syndecan-2 expression and melanoma cell migration and invasion in a melanin synthesis-independent manner. Furthermore, syndecan-2 overexpression rescued the migration defects induced by ␣-melanocyte-stimulating hormone treatment. Together, these data strongly suggest that syndecan-2 plays a crucial role in the migratory potential of melanoma cells.

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“…Moreover, it is well known that syndecans cooperate with integrins as co-receptors for fibronectin, which constitutes various types of ECM, and participate in cell adhesion and/or migration through regulation of focal contact and stress fiber formation (12)(13)(14)(15)(16). Furthermore, besides the function regarding this signal transduction, cell surface proteoglycans provide initial docking sites for the binding to various viruses (17,18).…”

mentioning

confidence: 99%

A Novel Function of Syndecan-2, Suppression of Matrix Metalloproteinase-2 Activation, Which Causes Suppression of Metastasis

Munesue

Yoshitomi

Kusano

et al. 2007

Journal of Biological Chemistry

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The syndecans comprise a family of cell surface heparan sulfate proteoglycans exhibiting complex biological functions involving the interaction of heparan sulfate side chains with a variety of soluble and insoluble heparin-binding extracellular ligands. Here we demonstrate an inverse correlation between the expression level of syndecan-2 and the metastatic potential of three clones derived from Lewis lung carcinoma 3LL. This correlation was proved to be a causal relationship, because transfection of syndecan-2 into the higher metastatic clone resulted in the suppression of both spontaneous and experimental metastases to the lung. Although the expression levels of matrix metalloproteinase-2 (MMP-2) and its cell surface activators, such as membrane-type 1 matrix metalloproteinase and tissue inhibitor of metalloproteinase-2, were similar regardless of the metastatic potentials of the clones, elevated activation of MMP-2 was observed in the higher metastatic clone. Removal of heparan sulfate from the cell surface of low metastatic cells by treatment with heparitinase-I promoted MMP-2 activation, and transfection of syndecan-2 into highly metastatic cells suppressed MMP-2 activation. Furthermore, transfection of mutated syndecan-2 lacking glycosaminoglycan attachment sites into highly metastatic cells did not have any suppressive effect on MMP-2 activation, suggesting that this suppression was mediated by the heparan sulfate side chains of syndecan-2. Actually, MMP-2 was found to exhibit a strong binding ability to heparin, the dissociation constant value being 62 nM. These results indicate a novel function of syndecan-2, which acts as a suppressor for MMP-2 activation, causing suppression of metastasis in at least the metastatic system used in the present study.Tumor metastasis is accomplished through a multistep process in which individual tumor cells disseminate from a primary tumor to distant secondary sites. In the process of metastasis, tumor cells are involved in numerous interactions with the extracellular matrix (ECM) 2 providing information that controls the behavior of tumor cells. The information inscribed in the ECM is transmitted to tumor cells through interaction between individual ECM ligands and the respective cell surface receptors.One class of cell surface receptors with such functions is cell surface heparan sulfate proteoglycans, including the transmembrane-type syndecan family and the glycosylphosphatidylinositol-anchored-type glypican family (1-3). However, cell surface heparan sulfate proteoglycans are unique and are different from proteinous cell surface receptors in terms of the binding redundancy for ligands. This is because the many ligand-binding sites reside in the polysaccharide moiety (i.e. heparan sulfate side chains). Therefore, theoretically, they can be receptors for all heparin-binding molecules. Actually, a large number of reports have demonstrated that cell surface heparan sulfate proteoglycans function as receptors for soluble heparinbinding ligands, such as cell growth factors...

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Participation of Syndecan 2 in the Induction of Stress Fiber Formation in Cooperation with Integrin α5β1: Structural Characteristics of Heparan Sulfate Chains with Avidity to COOH-Terminal Heparin-Binding Domain of Fibronectin

Cited by 92 publications

References 48 publications

Decreased syndecan-2 expression correlates with trichostatin-A induced-morphological changes and reduced tumorigenic activity in colon carcinoma cells

Decreased syndecan-2 expression correlates with trichostatin-A induced-morphological changes and reduced tumorigenic activity in colon carcinoma cells

Syndecan-2 Regulates the Migratory Potential of Melanoma Cells

A Novel Function of Syndecan-2, Suppression of Matrix Metalloproteinase-2 Activation, Which Causes Suppression of Metastasis

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