Involvement of adhesion molecules in metastasis of SW1990, human pancreatic cancer cells

Hosono, Jiro; Narita, Tetsuharu; Kimura, Naoko; Sato, Mikinori; Nakashio, Tatsuaki; Kasai, Yasushi; Nonami, Toshiaki; Nakao, Akimasa; Takagi, Hiroshi; Kannagi, Reiji

doi:10.1002/(sici)1096-9098(199802)67:2<77::aid-jso2>3.0.co;2-i

Cited by 46 publications

(29 citation statements)

References 22 publications

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“…The identification of CD44 and integrin ␣6 in this category (Table I) provided an opportunity to test whether any of the sialic acid-specific changes identified in the glycoproteomic data had a meaningful impact on cell behavior because of these molecules involvement in cancer progression and metastasis (23)(24)(25). Metastasis is a multistep process in which cancerous cells separate from the primary tissue and enter the circulatory system where they interact with various host cells before they migrate and lodge in the target organ and form secondary metastatic colonies.…”

Section: Flux-driven Sialylation Of Cd44 and Integrin ␣6 Enhancesmentioning

confidence: 99%

Metabolic Flux Increases Glycoprotein Sialylation: Implications for Cell Adhesion and Cancer Metastasis

Almaraz

Tian

Bhattarcharya

et al. 2012

Molecular & Cellular Proteomics

109

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This study reports a global glycoproteomic analysis of pancreatic cancer cells that describes how flux through the sialic acid biosynthetic pathway selectively modulates a subset of N-glycosylation sites found within cellular proteins. These results provide evidence that sialoglycoprotein patterns are not determined exclusively by the transcription of biosynthetic enzymes or the availability of N-glycan sequons; instead, bulk metabolic flux through the sialic acid pathway has a remarkable ability to increase the abundance of certain sialoglycoproteins while having a minimal impact on others. Specifically, of 82 glycoproteins identified through a mass spectrometry and bioinformatics approach, ϳ31% showed no change in sialylation, ϳ29% exhibited a modest increase, whereas ϳ40% experienced an increase of greater than twofold. The surfaces of mammalian cells are covered with a dense layer of carbohydrates, collectively known as the glycocalyx, that influence many aspects of the interaction between a cell and its microenvironment. To date, the biosynthesis of cell surface displayed glycans has been thought to be controlled largely by individual glycosyltransferases based on the assumption that flux through the metabolic pathways that supply activated nucleotide sugar donors (the substrates for these enzymes) is not a limiting factor. For example, this premise has been used in mathematical models of sialylation (1), where concentrations of CMP-Neu5Ac in the lumen of the Golgi were assumed to be much higher than the K m of sialyltransferases (2). In the past several years, the idea that nucleotide sugars, exemplified by CMP-Neu5Ac (shown in Fig. 1A), are not a limiting or controlling factor in glycosylation has garnered one major and unambiguous exception, notably that changes in flux through the hexosamine biosynthetic pathway (HBP) 1 can alter UDP-GlcNAc levels with profound consequences on the branching of N-linked glycans (3). By changing the valence of these glycoconjugates, flux through the HBP can alter the galectin lattice and affect a host of downstream biological events including cancer progression (4); cell differentiation and proliferation (3); and autoimmunity, metabolic syndromes, and aging (5).In this report, we demonstrate that the HBP is not unique in its ability to control surface glycoproteins via bulk metabolic flux. In particular, counter to earlier assumptions that flux through the sialic acid pathway does not significantly alter the sialylation of individual glycans (2), analysis of two "high-demand" sialoglycans (i.e. polysialylated NCAM (6) and podocalyxin (7)) suggested that fluctuations in the intracellular concentrations of sialic acid and the corresponding supply of CMP-Neu5Ac critically affected their production. In the current report, we used a global cell level approach to investigate whether these two examples were outliers or whether metabolic flux controls the surface display of sialic acid with fine resolution across a wide range of N-linked glycoproteins. We found that the sialylat...

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Section: Flux-driven Sialylation Of Cd44 and Integrin ␣6 Enhancesmentioning

confidence: 99%

Metabolic Flux Increases Glycoprotein Sialylation: Implications for Cell Adhesion and Cancer Metastasis

Almaraz

Tian

Bhattarcharya

et al. 2012

Molecular & Cellular Proteomics

109

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“…Monoclonal antibodies directed to the sialyl Lewis a/x determinants were shown to inhibit orthotopic metastasis of human pancreatic and gastric cancers in nude mice. 49,50) Screening of a random peptide library for peptides capable of binding to an anti-sialyl Lewis a antibody led to a sialyl Lewis a -mimetic peptide, which inhibited colonization of tumor cells expressing sialyl Lewis a . 51) The antisensecDNA approach, and more recently the iRNA approach, 52) would be promising strategies; use of antisense-cDNA for FUT7 gene was shown to significantly suppress sialyl Lewis x expression and cell adhesion in leukemia cells, 53) and its use for fucosyltransferase III/VI was shown to suppress colonization of colon cancer cells.…”

Section: Modulation Of the Selectin-mediated Cell Adhesion For Anti-mmentioning

confidence: 99%

Carbohydrate‐mediated cell adhesion in cancer metastasis and angiogenesis

et al. 2004

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“…We previously reported the dissemination of SW1990 in the abdominal cavity after intraperitoneal inoculation. 20 Human hepatocytes (hNHeps, Cambrex, Charles City, IA, USA), hepatocyte media and supplement (HCM Bullet kit, Cambrex) were purchased from Takara Bio Co. (Otsu, Japan). The normal liver cells were cultured in human hepatocyte media with HCM supplement.…”

Section: Cell Linesmentioning

confidence: 99%

Suitability of a US3-inactivated HSV mutant (L1BR1) as an oncolytic virus for pancreatic cancer therapy

Kasuya¹,

Nishiyama

Nomoto³

et al. 2007

Cancer Gene Ther

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Recently, the use of oncolytic viruses against cancer has attracted considerable attention. We studied the potential of the US3 locusdeficient herpes simplex virus (HSV), L1BR1, for oncolytic virus therapy. Its high specificity and potency indicate that L1BR1 is a promising candidate as a new oncolytic virus against pancreatic cancer. Moreover, the virus exhibited the unique characteristic of increasing apoptosis when used in combination with anticancer drugs. We assessed the feasibility of using the US3 locus-deficient HSV named L1BR1 as a new replication-competent oncolytic virus for the treatment of pancreatic cancer. The US3 locus of HSV has been shown to be a key gene in producing a multifunctional protein kinase that inhibits apoptosis induced by viral infections, chemicals and ultraviolet (UV) light. L1BR1 has been reported to be more than 10 000-fold less virulent than the parental virus in mice. In this study, we examined the tumor specificity and oncolytic effect of this attenuated replication-competent virus, L1BR1, in pancreatic cancers derived from SW1990, Capan2 and Bxpc-3cells compared with the parent virus and other well-known oncolytic herpes viruses (R3616 and hrR3). We also studied the efficacy of L1BR1 for the induction of apoptosis as an attribute of this virus in combination with the anticancer drugs 5FU and cisplatin. The combined treatment of the pancreatic cancer cells with L1BR1 and these anticancer drugs enhanced apoptosis significantly. More importantly, L1BR1 showed the lowest replication capacity in normal human hepatocytes, but the highest tumor-reducing effect in vivo among the oncolytic herpes viruses tested. In addition, L1BR1 significantly increased the induction of apoptosis of cancer cells when treated in combination with anticancer drugs although the parental virus inhibited the induction of apoptosis. These results suggest that L1BR1 is promising as a new anticancer oncolytic virus.

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Involvement of adhesion molecules in metastasis of SW1990, human pancreatic cancer cells

Cited by 46 publications

References 22 publications

Metabolic Flux Increases Glycoprotein Sialylation: Implications for Cell Adhesion and Cancer Metastasis

Metabolic Flux Increases Glycoprotein Sialylation: Implications for Cell Adhesion and Cancer Metastasis

Carbohydrate‐mediated cell adhesion in cancer metastasis and angiogenesis

Suitability of a US3-inactivated HSV mutant (L1BR1) as an oncolytic virus for pancreatic cancer therapy

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