N-linked oligosaccharide processing and autocrine stimulation of tumor cell proliferation

VanderElst, Ingrid; Dennis, James W.

doi:10.1016/0014-4827(91)90083-7

Cited by 18 publications

(10 citation statements)

References 27 publications

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“…Similarly in human uroepithelial cell lines, increased branching of complex-type asparagine-linked oligosaccharides was correlated with the degree of transformation and invasiveness (Debray et al 1986). Loss or truncation of b1-6 branched oligosaccharides has multiple eects on cellular phenotypes, including decreased adhesion to vascular endothelial cells, increased adhesion to extracellular matrix proteins (Dennis et al 1982), reduced cellular motility and invasion of the extracellular matrix (Yagel et al 1990), reduced cellular response to autocrine growth stimulation (Dennis et al 1990;VanderElst and Dennis 1991) and increased susceptibility to natural killer cells (Ahrens and Ankel 1987;Dennis and Laferte 1985).…”

Section: Discussionmentioning

confidence: 96%

Elevated activity of N -acetylglucosaminyltransferase V in human hepatocellular carcinoma

Yao

Zhou

Jiang

et al. 1998

Journal of Cancer Research and Clinical Oncology

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Cell-surface glycoproteins are regarded as candidates for involvement in the spread of tumor cells. N-linked beta1-6 branched oligosaccharides may contribute directly to the malignant or metastatic phenotypes of tumor cells. Increased beta1-6 branching has been associated with an increased level of N-acetylglucosaminyltransferase V (GlcNAc transferase V), the glycosyltransferase that initiates the beta1-6 branching. In this report, 33 pathologically verified hepatocellular carcinoma (HCC) specimens, six non-cancerous tissues surrounding HCC and five normal liver specimens have been studied. We have quantified N-linked beta1-6 branched oligosaccharides indirectly by measuring GlcNac transferase V activity. The average GlcNac transferase V activities in hepatocellular carcinoma (HCC), noncancerous tissues surrounding HCC and normal liver tissues were 324.2 +/- 269.8, 84.8 +/- 20.7 and 7.0 +/- 6.2 pmol product h(-1) mg protein(-1) (P < 0.05) respectively. In addition, the activity was correlated with the TNM classification of HCC. The average activities of GlcNAc transferase V in stages T1, T2-3 and T4 were 77.6 +/- 57.8, 369.0 +/- 294.7 and 329.9 +/- 205.9 pmol product h(-1) mg protein h(-1) respectively (P < 0.05), showing that the activity of the enzyme in advanced HCC was higher than that in early HCC. Our preliminary results indicated that GlcNAc transferase V activity increased in human HCC and was correlated with its progression.

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Section: Discussionmentioning

confidence: 96%

Elevated activity of N -acetylglucosaminyltransferase V in human hepatocellular carcinoma

Yao

Zhou

Jiang

et al. 1998

Journal of Cancer Research and Clinical Oncology

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“…1). The concentration of swainsonine used in these experiments is approximately 20-fold higher than the Ki for inhibition of pl-6 branched oligosaccharides and therefore results in optimal inhibition of N-linked processing (i.e., approximately 80%) (VanderElst and Dennis, 1991). Swainsonine does not reduce plating efficiency, and tumor cells can be cultured in the presence of the drug for weeks with no evidence of toxicity.…”

Section: Resultsmentioning

confidence: 99%

“…For example, recombinant erythropoietin with bi-antennary Nlinked oligosaccharides has been shown to be more active in vitro than the same glycoprotein bearing tri-and tetraantennary oligosaccharides (Takeuchi et al, 1989). The malignant tumor cell lines used in this study have been shown to secrete growth-factor activity which enhances tumor-cell proliferation VanderElst and Dennis, 1991;Korczak et al, 1991), and for A3a mammary-carcinoma cells, autocrine factor(s) also increase stromelysin and decrease TIMP gene expression (Korczak et a/., 1991). It is possible that inhibition of oligosaccharide processing affects the activity of an autocrine factor, of its receptor or of a glycoprotein involved in the response to an autocrine factor.…”

Section: Discussionmentioning

confidence: 96%

“…In support of this relationship, it has been found that metastatic tumor cells cultured in the presence of Nlinked processing inhibitors (e.g., castanospermine and swainsonine), which act prior to the initiation of the Pl-6 linked antenna, lost their ability to metastasize (Dennis, 19866;Humphries et al, 1986;Pulverer et al, 1988;Kino et al, 1985). Furthermore, dramatic losses of metastatic potential have been observed in specific genetic classes of tumor-cell glycosylation mutants (Dennis et al, 1987).Loss or truncation of pl-6 branched oligosaccharides in metastatic tumor cells has pleiotropic effects on cellular phenotype, including increased adhesion to extracellular matrix (ECM) proteins (Dennis et ul., 1982), decreased adhesion to microvascular endothelial cells (Cornil et al, 1990), reduced cell motility and invasion into ECM in vitro Seftor et al, 1991), and reduced cellular response to autocrine growth stimulation VanderElst and Dennis, 1991). These phenotypic changes are common to tumor cells bearing glycosylation mutations that reduce metastatic potential and to wild-type tumor cells treated with the a-mannosidase-I1 inhibitor swainsonine.…”

mentioning

confidence: 99%

“…Loss or truncation of pl-6 branched oligosaccharides in metastatic tumor cells has pleiotropic effects on cellular phenotype, including increased adhesion to extracellular matrix (ECM) proteins (Dennis et ul., 1982), decreased adhesion to microvascular endothelial cells (Cornil et al, 1990), reduced cell motility and invasion into ECM in vitro Seftor et al, 1991), and reduced cellular response to autocrine growth stimulation VanderElst and Dennis, 1991). These phenotypic changes are common to tumor cells bearing glycosylation mutations that reduce metastatic potential and to wild-type tumor cells treated with the a-mannosidase-I1 inhibitor swainsonine.…”

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confidence: 99%

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Inhibition of N‐linked oligosaccharide processing in tumor cells is associated with enhanced tissue inhibitor of metalloproteinases (TIMP) gene expression

Korczak

Dennis

1993

Intl Journal of Cancer

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Previous studies on tumor-cell glycosylation mutants and drugs which inhibit oligosaccharide processing suggest that expression of sialylated and highly branched complex-type N-linked oligosaccharides is required for efficient tumor-cell metastasis. These observations prompted the present investigation, in order to determine whether loss of sialylated and highly branched complex-type oligosaccharide in cellular glycoproteins might affect the expression of genes, particularly of genes which can influence the malignant phenotypes. Swainsonine, an inhibitor of Golgi alpha-mannosidase II, has previously been shown to inhibit invasion in vitro and reduces solid tumor in vivo. Metastatic sub-lines of the SP1 murine mammary carcinoma cells cultured in the presence of swainsonine for 48 hr showed approximately 3-fold enhancement of TIMP mRNA levels, while urokinase (uPA) transcripts remained unchanged. To determine whether swainsonine's effect on TIMP mRNA levels was related to inhibition of oligosaccharide processing, we examined somatic glycosylation mutants with processing defects which attenuate metastatic potential. The Golgi UDP-Gal transport defect in murine MDAY-D2 lymphoma cells, Chinese hamster ovary cells (CHO) and human MeWo melanoma cells (i.e., D35W25, Lec8, 3S5 cell lines, respectively) was associated with increased TIMP mRNA levels. A revertant of Lec8 showed a return to the wild-type levels of TIMP mRNA, consistent with a causal relationship between the glycosylation mutation and TIMP gene expression. Similarly, CHO and MDAY-D2 mutants defective in GlcNAc-TV (i.e., Lec4 and KBL-1 respectively), which also reduces metastatic potential, showed increases in TIMP transcript levels. Nuclear run-on assays showed that transcription of the TIMP gene was increased in cells where N-linked oligosaccharide processing was inhibited either by swainsonine or by a glycosylation mutation. The results suggest that cell-specific patterns of glycoprotein glycosylation in human, murine and hamster cell lines affects the transcription of select genes, including TIMP, which may influence the invasive phenotype.

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Bitter Sweetness of Complexity

Horst

Wagener

2008

Glycoscience and Microbial Adhesion

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Glycosylation of proteins, lipids and mucins has gained increasing complexity in the course of evolution. Metazoans and mammals exhibit extensively exploited pathways of N-glycan biosynthesis, with unique features that are not found in plants or protozoans.Paralleling the complexity of N-glycan structure, their impact on regulatory processes has become very diverse and has evolved into a multidimensional lattice imprinting modes of cellular communication. Processes that are regulated by N-glycans are cellular adhesion and motility, growth factor and cytokine signalling, metabolic homeostasis, and binding of certain pathogens. Consequently, alterations in N-glycan biosynthesis interfere with cellular proliferation and differentiation and may produce disturbances in embryonic development, trigger inflammatory processes, favour tumour development and enhance the metastastic dissemination of primary tumours. Particular N-glycans that have been causally related to these pathological scenarios are the complex-type N-glycans, branching from oligomannosidic core structures into β-glycosidic linkages, connected to acetylated glucosamine and galactose, and yield extended lactosamine chains of variable length. These N-acetyllactosamines are preferred building blocks for further modification by fucosylation, sialylation, and sulphation, thus creating binding sites for different galectins or selectins. The focus of this review will be on the b1,6-N -acetylglucosaminyltransferase-V/GnT-V/MGAT5, a phylogenically conserved enzyme that is required for the synthesis of β1,6-branched complex-type oligosaccharides in the medial Golgi compartment, and its implications in metabolism and cancer progression.

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N-linked oligosaccharide processing and autocrine stimulation of tumor cell proliferation

Cited by 18 publications

References 27 publications

Elevated activity of N -acetylglucosaminyltransferase V in human hepatocellular carcinoma

Elevated activity of N -acetylglucosaminyltransferase V in human hepatocellular carcinoma

Inhibition of N‐linked oligosaccharide processing in tumor cells is associated with enhanced tissue inhibitor of metalloproteinases (TIMP) gene expression

Bitter Sweetness of Complexity

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