Expression of the neural cell adhesion molecule in astrocytic tumors

Sasaki, Hidenao; Yoshida, Kazunari; Ikeda, Eiji; Asou, Hiroaki; Inaba, Makoto; Otani, Mitsuhiro; Kawase, Takeshi

doi:10.1002/(sici)1097-0142(19980515)82:10<1921::aid-cncr16>3.0.co;2-v

Cited by 64 publications

(10 citation statements)

References 27 publications

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“…Indeed, tumor cells expressing the anti-NCAM intrabody showed metastatic behavior similar as the control tumor cells. This confirms the published data that abolished NCAM on the surface of tumor cells promotes metastasis [56, 66, 67]. Recently it was found that other cell surface proteins as NCAM can be polysialylated (i.e.…”

Section: Discussionsupporting

confidence: 91%

Intrabodies against the Polysialyltransferases ST8SiaII and ST8SiaIV inhibit Polysialylation of NCAM in rhabdomyosarcoma tumor cells

et al. 2017

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BackgroundPolysialic acid (polySia) is a carbohydrate modification of the neural cell adhesion molecule (NCAM), which is implicated in neural differentiation and plays an important role in tumor development and metastasis. Polysialylation of NCAM is mediated by two Golgi-resident polysialyltransferases (polyST) ST8SiaII and ST8SiaIV. Intracellular antibodies (intrabodies; IB) expressed inside the ER and retaining proteins passing the ER such as cell surface receptors or secretory proteins provide an efficient means of protein knockdown. To inhibit the function of ST8SiaII and ST8SiaIV specific ER IBs were generated starting from two corresponding hybridoma clones. Both IBs αST8SiaII-IB and αST8SiaIV-IB were constructed in the scFv format and their functions characterized in vitro and in vivo.ResultsIBs directed against the polySTs prevented the translocation of the enzymes from the ER to the Golgi-apparatus. Co-immunoprecipitation of ST8SiaII and ST8SiaIV with the corresponding IBs confirmed the intracellular interaction with their cognate antigens. In CHO cells overexpressing ST8SiaII and ST8SiaIV, respectively, the transfection with αST8SiaII-IB or αST8SiaIV-IB inhibited significantly the cell surface expression of polysialylated NCAM. Furthermore stable expression of ST8SiaII-IB, ST8SiaIV-IB and luciferase in the rhabdomyosarcoma cell line TE671 reduced cell surface expression of polySia and delayed tumor growth if cells were xenografted into C57BL/6 J RAG-2 mice.ConclusionData obtained strongly indicate that αST8SiaII-IB and αST8SiaIV-IB are promising experimental tools to analyze the individual role of the two enzymes during brain development and during migration and proliferation of tumor cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s12896-017-0360-7) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 91%

Intrabodies against the Polysialyltransferases ST8SiaII and ST8SiaIV inhibit Polysialylation of NCAM in rhabdomyosarcoma tumor cells

et al. 2017

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“…Cell adhesion molecules of the Ig superfamily are recognized increasingly for their association with cancer and malignant gliomas in particular (25,26). A close relative of CD155 in rodents, the tumor-associated glycoprotein E4, has been identified because of its association with gastrointestinal malignancies (27).…”

Section: Resultsmentioning

confidence: 99%

Intergeneric poliovirus recombinants for the treatment of malignant glioma

Gromeier

Lachmann²,

Rosenfeld³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

338

307

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Poliovirus neuropathogenicity depends on sequences within the 5 nontranslated region of the virus. Exchange of the poliovirus internal ribosomal entry site with its counterpart from human rhinovirus type 2 resulted in attenuation of neurovirulence in primates. Despite deficient virus propagation in cells of neuronal origin, nonpathogenic polio recombinants retain excellent growth characteristics in cell lines derived from glial neoplasms. Susceptibility of malignant glioma cells to poliovirus may be mediated by expression of a poliovirus receptor, CD155, in glial neoplasms. Intergeneric polio recombinants with heterologous internal ribosomal entry site elements unfolded strong oncolytic potential against experimentally induced gliomas in athymic mice. Our observations suggest that highly attenuated poliovirus recombinants may have applicability as biotherapeutic antineoplastic agents.M alignant gliomas are the most common primary tumors of the central nervous system (1). Available treatment is of limited utility for these tumors, and prognosis is therefore poor (1). The resistance of malignant gliomas to conventional therapies has inspired the search for novel strategies, and recently, these strategies have involved animal viruses, either as attenuated variants of pathogenic species with direct oncolytic properties (2, 3) or as delivery vehicles for foreign genetic material (4 -6).Poliovirus is a nonenveloped plus-stranded RNA virus belonging to Picornaviridae and is the causative agent of paralytic poliomyelitis. The vast majority of poliovirus infections remain asymptomatic, but 1-2% of cases result in neurologic complications (7). Restriction of poliovirus cell tropism to lower motor neurons resident within the spinal cord and brainstem gives rise to a highly characteristic clinical syndrome dominated by flaccid paralysis. Selective targeting of motor neurons by poliovirus is most likely determined by the distribution of its cellular receptor, the Ig superfamily molecule CD155. This assumption is supported by the observation that mice transgenic for CD155 develop a polio-like syndrome after poliovirus infection (8-10). In addition, cell-internal conditions favoring viral replication may contribute to poliovirus cell-type specificity.The neuropathogenicity of poliovirus depends on the celltype-specific function of its internal ribosomal entry site (IRES) element in cells of neuronal origin (10). The IRES is part of the 5Ј nontranslated region not only of picornaviruses (11) but also of hepatitis C virus (12, 13). IRES elements assure initiation of translation in a 5Ј end-independent, cap-independent manner (14-16). We have demonstrated that IRES elements encode strong cell-type-specific restrictions toward virus propagation.This restriction is illustrated by the highly attenuated phenotype of intergeneric recombinant polioviruses carrying IRES elements derived from human rhinovirus type 2 (10, 17). We have demonstrated that a prototype intergeneric poliovirus chimera [called PV1(RIPO)] is characterized by exce...

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“…High expression levels of 90K are associated with a shorter survival, the occurrence of metastasis or a reduced response to chemotherapy in patients with different types of malignancy [66]. Other proteins overexpressed in astrocytomas have also been implicated in tumor growth and invasion, such as the inter-cellular adhesion molecule 1 (ICAM-1) [67], the neural cell adhesion molecule NCAM1 [68] and the thrombomodulin (THBD) [69]. The polysialylated form of the cell surface glycoprotein neural cell adhesion molecule (PSA-NCAM) is overexpressed in human GBM and is considered as an adverse prognostic factor for GBM patients [70].…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Tumor-Associated Cell Surface Sialoglycoproteins in Human Glioblastoma Tumors Using Quantitative Proteomics

et al. 2014

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Glioblastoma multiform (GBM) remains clinical indication with significant “unmet medical need”. Innovative new therapy to eliminate residual tumor cells and prevent tumor recurrences is critically needed for this deadly disease. A major challenge of GBM research has been the identification of novel molecular therapeutic targets and accurate diagnostic/prognostic biomarkers. Many of the current clinical therapeutic targets of immunotoxins and ligand-directed toxins for high-grade glioma (HGG) cells are surface sialylated glycoproteins. Therefore, methods that systematically and quantitatively analyze cell surface sialoglycoproteins in human clinical tumor samples would be useful for the identification of potential diagnostic markers and therapeutic targets for malignant gliomas. In this study, we used the bioorthogonal chemical reporter strategy (BOCR) in combination with label-free quantitative mass spectrometry (LFQ-MS) to characterize and accurately quantify the individual cell surface sialoproteome in human GBM tissues, in fetal, adult human astrocytes, and in human neural progenitor cells (NPCs). We identified and quantified a total of 843 proteins, including 801 glycoproteins. Among the 843 proteins, 606 (72%) are known cell surface or secreted glycoproteins, including 156 CD-antigens, all major classes of cell surface receptor proteins, transporters, and adhesion proteins. Our findings identified several known as well as new cell surface antigens whose expression is predominantly restricted to human GBM tumors as confirmed by microarray transcription profiling, quantitative RT-PCR and immunohistochemical staining. This report presents the comprehensive identification of new biomarkers and therapeutic targets for the treatment of malignant gliomas using quantitative sialoglycoproteomics with clinically relevant, patient derived primary glioma cells.

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Expression of the neural cell adhesion molecule in astrocytic tumors

Abstract: To the authors' knowledge, this study provides the first direct evidence that NCAM is down-regulated in the development of the malignancy of astrocytic tumors; and it is suggested that reduced NCAM expression might be involved in the development of biologic malignancy.

Cited by 64 publications

References 27 publications

Intrabodies against the Polysialyltransferases ST8SiaII and ST8SiaIV inhibit Polysialylation of NCAM in rhabdomyosarcoma tumor cells

Intrabodies against the Polysialyltransferases ST8SiaII and ST8SiaIV inhibit Polysialylation of NCAM in rhabdomyosarcoma tumor cells

Intergeneric poliovirus recombinants for the treatment of malignant glioma

Identification of Novel Tumor-Associated Cell Surface Sialoglycoproteins in Human Glioblastoma Tumors Using Quantitative Proteomics

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