Localisation of specific heparan sulfate proteoglycans during the proliferative phase of brain development

Ford-Perriss, Miriam; Turner, Kirsty; Guimond, Scott E.; Apedaile, Anwyn; Haubeck, H.-D.; Turnbull, Jeremy E.; Murphy, Mark

doi:10.1002/dvdy.10298

Cited by 98 publications

(72 citation statements)

References 89 publications

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“…Indeed, in accordance with this line of speculation, syndecan-1 has been shown to be involved in proliferative phases 37 and correlated with enhanced tumorigenic potential in different cell types. 23 To that end, we showed by altering the expression level of syndecan-1 that overexpression of syndecan-1 renders cancer cells more proliferative and anchorage-independent while silencing syndecan-1 disrupted proliferativeness of HEC-1A cells.…”

supporting

confidence: 67%

Syndecan‐1, a key regulator of cell viability in endometrial cancer

Choi

Kim

Ryu

et al. 2007

Intl Journal of Cancer

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Syndecan-1 is one of the major proteoglycans on cell surfaces involved in major biological processes. Although loss of syndecan-1 correlates well with the gain of cancerous characteristics in a wide range of cancers, increased expression of syndecan-1 also coincides with adverse outcomes in some cancers, including breast, ovarian and pancreatic cancers. For this Janus-faced attitude of syndecan-1, we sought to examine expression patterns of syndecan-1 in endometrial carcinoma (EC) and gain insight into the roles of syndecan-1. Immunohistochemical examinations of 109 endometrial tissue samples from myoma, hyperplasia and EC uteri revealed that syndecan-1 expression was significantly upregulated in EC compared with hyperplasia (p < 0.001). To evaluate pathophysiological functions of syndecan-1, its expression level was altered, and subsequent outcomes were examined using human endometrial cancer cell lines such as HEC-1A, AN3CA and KLE cells. Overexpression of syndecan-1 increased the growth of HEC-1A cells regardless of anchorage dependence while silencing syndecan-1 by antisense RNAs caused apoptotic cell death. Consistent with decreased viability, the loss of syndecan-1 was also accompanied by a decrease in the activation of Erk and Akt and a concomitant decrease in the phosphorylation of PTEN and PDK1, which are known as negative and positive regulators of Akt activation, respectively. These down-regulatory effects were reversed upon overexpression of syndecan-1. Collectively together, the aforementioned findings lend support to the notion that upregulation of syndecan-1 may be a critical element for endometrial cancers in maintaining their viability and thus can serve as a cancer specific therapeutic and diagnostic marker. ' 2007 Wiley-Liss, Inc.Key words: endometrial cancers; syndecan-1; apoptotic cell death; Erk/Akt pathway Endometrial carcinoma (EC) is the world's 7th most frequent malignancy with a much higher rate of incidence in well-developed countries.1 In the United States alone, a little over 41,200 women develop EC, and about 7,350 women die from this malignancy each year.2 Though there are multitudes of possible oncogenic abnormalities throughout cancer development, EC can be characterized with a certain number of frequent genetic alterations or regulation of gene expression. Mutations and overexpression of k-ras, steroid hormone receptors, PTEN, Her2/neu and p53 are common abnormalities in EC.3-6 Moreover, recent findings showed that atypical expression of cell surface proteins participating in the cell-cell or the cell-matrix interaction can help progression of endometrial cancer. 5,7,8 Consequently, these abnormalities contribute to the altered expression of proteins involved in cell cycle regulation and survival. 9,10 Syndecan is a four-membered cell membrane proteoglycan that shows a heavy modification on its ectodomain with heparan sulfate (HS) glucosaminoglycan chains. As a cell surface receptor, it shows a deep involvement in both normal and pathological events by regulating the cell-cell ...

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supporting

confidence: 67%

Syndecan‐1, a key regulator of cell viability in endometrial cancer

Choi

Kim

Ryu

et al. 2007

Intl Journal of Cancer

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“…We present the first evidence that (1) functional DG receptors are found on oligodendrocyte cell surfaces, and that, (2) by blocking DG interactions either in oligodendrocytes on laminin substrates or in oligodendrocyte-neuron co-cultures, the ability of oligodendrocytes to differentiate and to myelinate is perturbed. DG has also been shown to mediate interactions with several other extracellular molecules that are expressed in the brain, including agrin, perlecan and ␣-neurexin (Ford-Perriss et al, 2003;Gesemann et al, 1998;Halfter, 1993;Maresh et al, 1996;Sugita et al, 2001). Of these ligands, however, only laminins have been shown to play a role in regulating CNS myelination to date, and we suggest that the dysmyelination associated with laminin deficiency is likely to involve the disruption of at least two classes of receptor interactions: integrin and DG.…”

Section: Discussionmentioning

confidence: 80%

Identification of dystroglycan as a second laminin receptor in oligodendrocytes, with a role in myelination

et al. 2007

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2Developmental abnormalities of myelination are observed in the brains of laminin-deficient humans and mice. The mechanisms by which these defects occur remain unknown. It has been proposed that, given their central role in mediating extracellular matrix (ECM) interactions, integrin receptors are likely to be involved. However, it is a non-integrin ECM receptor, dystroglycan, that provides the key linkage between the dystrophin-glycoprotein complex (DGC) and laminin in skeletal muscle basal lamina, such that disruption of this bridge results in muscular dystrophy. In addition, the loss of dystroglycan from Schwann cells causes myelin instability and disorganization of the nodes of Ranvier. To date, it is unknown whether dystroglycan plays a role during central nervous system (CNS) myelination. Here, we report that the myelinating glia of the CNS, oligodendrocytes, express and use dystroglycan receptors to regulate myelin formation. In the absence of normal dystroglycan expression, primary oligodendrocytes showed substantial deficits in their ability to differentiate and to produce normal levels of myelin-specific proteins. After blocking the function of dystroglycan receptors, oligodendrocytes failed both to produce complex myelin membrane sheets and to initiate myelinating segments when co-cultured with dorsal root ganglion neurons. By contrast, enhanced oligodendrocyte survival in response to the ECM, in conjunction with growth factors, was dependent on interactions with beta-1 integrins and did not require dystroglycan. Together, these results indicate that laminins are likely to regulate CNS myelination by interacting with both integrin receptors and dystroglycan receptors, and that oligodendrocyte dystroglycan receptors may have a specific role in regulating terminal stages of myelination, such as myelin membrane production, growth, or stability.

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“…Indeed, during an early phase of mouse brain development, the different syndecan family members, as well as the HS-modifying enzymes, show tightly regulated spatiotemporal expression patterns (Ford-Perriss, 2003;Sedita et al, 2004).…”

Section: Regulation By Specific Sugar Modificationsmentioning

confidence: 99%

Syndecan regulates cell migration and axon guidance inC. elegans

et al. 2005

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During nervous system development, axons that grow out simultaneously in the same extracellular environment are often sorted to different target destinations. As there is only a restricted set of guidance cues known,regulatory mechanisms are likely to play a crucial role in controlling cell migration and axonal pathfinding. Heparan sulfate proteoglycans (HSPGs) carry long chains of differentially modified sugar residues that have been proposed to encode specific information for nervous system development. Here, we show that the cell surface proteoglycan syndecan SDN-1 functions autonomously in neurons to control the neural migration and guidance choices of outgrowing axons. Epistasis analysis suggests that heparan sulfate (HS) attached to SDN-1 can regulate guidance signaling by the Slit/Robo pathway. Furthermore, SDN-1 acts in parallel with other HSPG core proteins whose HS side chains are modified by the C5-epimerase HSE-5, and/or the 2O-sulfotransferase HST-2, depending on the cellular context. Taken together, our experiments show that distinct HS modification patterns on SDN-1 are involved in regulating axon guidance and cell migration in C. elegans.

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Localisation of specific heparan sulfate proteoglycans during the proliferative phase of brain development

Cited by 98 publications

References 89 publications

Syndecan‐1, a key regulator of cell viability in endometrial cancer

Syndecan‐1, a key regulator of cell viability in endometrial cancer

Identification of dystroglycan as a second laminin receptor in oligodendrocytes, with a role in myelination

Syndecan regulates cell migration and axon guidance inC. elegans

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