Alterations in the glycolipid composition and cellular properties of ovarian carcinoma‐derived RMG‐1 cells on transfection of the α1,2‐fucosyltransferase gene

Iwamori, Masao; Tanaka, Kyoko; Kubushiro, Kaneyuki; Lin, Bei; Kiguchi, Kazushige; Ishiwata, Isamu; Tsukazaki, Katsumi; Nozawa, Shiro

doi:10.1111/j.1349-7006.2005.00005.x

Cited by 50 publications

(54 citation statements)

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“…7, since the syntheses of IV 6 NeuAcα-nLc 4 Cer and Lewis-active glycolipids occur with the same substrate at the branch of the lacto-series pathway, our findings suggest that the synthesis of lacto-series glycolipids is influenced by the availability of substrate glycolipids in individual steps of glycosyltransferase reactions. As reported in our previous paper (8), when the activity of α1,2-fucosyltransferase in ovarian carcinoma-derived RMG-1 cells increased to 20-30 fold that in the original cells on transfection with the α1,2-fucosyltransferase gene, the amount of Le Y increased to 10-fold of the original level. On the other hand, sialylated glycolipids in the original cells, including sialyl Le X and IV 3 NeuAcα-nLc 4 Cer, were absent in the transfectants, suggesting that the enhanced fucosylation of Le X and nLc 4 Cer at the terminal step of glycosylation inhibits their sialylation through deprivation of the substrate.…”

Section: Discussionsupporting

confidence: 81%

“…Transfection of the α1,2-fucosyltransferase gene into RMG-1 cells resulted in increases in Le Y and H-1 glycolipids, and a concomitant decrease in sialylated glycolipids. The transfectants exhibited increased adhesion with mesothelial cells and resistance against an anticancer drug, 5-fluorouracil, in comparison to those of RMG-1 cells (7,8). In addition, significant changes in glycolipids including Lewis-active ones were observed in ovarian carcinoma-derived KF28 cells exhibiting anticancer drug-resistance to cisplatin and taxol, probably due to an alteration of the activities of transporter proteins in regard to the excretion of drugs in glycolipid-rich membrane rafts (9,10).…”

Section: Introductionmentioning

confidence: 99%

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Expression of α2,6-sialic acid-containing and Lewis-active glycolipids in several types of human ovarian carcinomas

et al. 2010

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Abstract.To identify glycolipid antigens associated with histologically defined types of ovarian carcinomas, we determined the amounts of α2,6-sialyl and Lewis-active glycolipids, the specific activities of the α2,3-and α2,6-sialyltransferases, and the gene expression of sugar transferases in mucinous and serous cystadenocarcinoma, clear cell adenocarcinoma and endometrioid carcinoma tissues and cell lines derived from them. α2,6-sialyl glycolipid IV 6 NeuAcα-nLc 4 Cer detected with a newly developed monoclonal antibody, Y916, was present in 5/7 serous cystadenocarcinoma cases in relatively higher amounts than those in the other carcinoma tissues. On the other hand, the amounts of Lewis-active glycolipids in serous cystadenocarcinoma tissues were lower than those in the other carcinoma tissues. No correlation was observed between the structures of Lewis glycolipids and the histological classification. The gene expression of α2,3-and α2,6-sialyltransferases and α1,3/4-fucosyltransferase for the synthesis of Lewis-active glycolipids was not positively correlated with the amounts of the respective glycolipids, probably due to the epigenetic regulation of transferases in the overall metabolic pathways for lacto-series glycolipids. However, the amounts of GM3 and GD3 with short carbohydrate chains correlated with the relative intensities of GM3 and GD3 synthase gene expression, respectively. Among ovarian carcinoma-derived cell lines, the serous cystadenocarcinoma-derived ones exhibited a lower frequency of Lewis-active glycolipid expression than the other carcinoma-derived ones, which was similar to that in the respective tissues. Thus, malignancy-related Lewisactive glycolipids were shown to be regulated in different modes in ovarian serous cystadenocarcinomas and the other carcinomas.

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Expression of α2,6-sialic acid-containing and Lewis-active glycolipids in several types of human ovarian carcinomas

et al. 2010

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“…sialyl Le a antigen for diagnosis of pancreatic, gallbladder and colon carcinomas [5,6], and Le b , Le Y and H antigens for prediction of metastatic potential [7][8][9]. We have also observed that Le X and Le b are characteristically expressed in ovarian serous carcinoma KF28 cells exhibiting anti-cancer drug resistance, and enhanced expression of Le Y in ovarian clear cell carcinoma RMG-1 cells on transfection of α1,2-fucosyltransferase results in high dissemination potential and anti-cancer drug resistance [10,11]. On comparison of glycolipid compositions between KF28 cells and KF28-derived anticancer drug-resistant cells, and between RMG-1 cells and fucosyltransferase gene-transfected RMG-1 cells, globo-, lacto-and neolacto-series glycolipid profiles were found to be characteristically changed to cause alteration of the antigenicity of glycolipids, and their cellular functions including in anticancer drug-resistance and peritoneal dissemination [11,12].…”

Section: Introductionmentioning

confidence: 79%

Enhanced expression of unique gangliosides with GM2-determinant in human uterine cervical carcinoma-derived cell lines

et al. 2016

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Monoclonal antibody YHD-06 generated by immunization with GM2 reacted with gangliosides with GM2-determinant, i.e., GM2, GalNAc-GM1b and GalNAc-GD1a, among which GalNAc-GD1a was characterized as an antigen of autoimmune peripheral neuropathies including Guillain-Barré syndrome. When glycolipids were examined by TLC-immunostaining with YHD-06 in seven human cervical carcinoma-derived cell lines, GM2 was found in all cell lines, amounting to 15.5 % to 57.5 % of total gangliosides. Whereas GalNAc-GD1a was present in three cell lines, amounting to 5.4-17.5 % of total gangliosides, and GalNAc-GM1b in four cell lines in amounts of less than 2 %. The elevated amounts of gangliosides with GM2 determinant were closely correlated with the relative intensities of gene expression of GalNAc transferase, this being characteristic of cervical carcinoma-derived cells. However, in tissues from patients with several histological types of cervical carcinomas, GM3 was ubiquitously expressed in amounts of more than 66 % of total gangliosides, GM2 was expressed in only five of 15 tissues, and both GalNAc-GM1b and GalNAc-GD1a were not even detected in trace amounts. Since GM1 was detected in all tissues in amounts of less than 0.06 μg/mg dried tissue, all cervical carcinoma tissues were revealed to exhibit GM2 synthesis, indicating that enhanced synthesis of gangliosides with GM2 determinant is a characteristic of cultivated cells in vitro. Similarly, although I(3)SO3-GalCer was not present in the squamous cell carcinoma (SCC) tissues, SCC-derived cells selectively expressed II(3)SO3-LacCer. Since enhanced synthesis of GM2 has been reported in SV-40 virus-transfected fibroblasts, papilloma virus might be involved in the expression of GM2 in cervical carcinoma-derived cells.

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Section: Research Article Open Accessmentioning

confidence: 99%

“…Also, increased expression of LeY antigen and CD44 were associated with elevated resistance to chemotherapeutic drugs such as platinum agents, taxanes, 5-fluorouracil, doxorubicin and mitomycin [9][10][11][12].Although the effects of alternative splicing and post-translational glycosylation of CD44 on its interaction with HA have been studied in several tumor types, few data has described the effect of these alterations in LACSCC. The aim of this study is to evaluate the role of CD44 and LeY antigen in the outcome LACSCC patients.…”

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Relevant Role of Di-Fucosylated Ley Antigen in the Outcome of Locally Advanced Cervical Squamous Cell Carcinoma Patients Treated with Cisplatin Regimen

Zwenger¹,

Leone²,

Je³

et al. 2015

Transl Med (sunnyvale)

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Research Article Open AccessRecently, Gao et al. found that the di-fucosylated Lewis Y (LeY) antigen is part of the composition of CD44 and their increased expression is correlated with enhanced CD44-mediated cell adhesion and migration [8]. Also, increased expression of LeY antigen and CD44 were associated with elevated resistance to chemotherapeutic drugs such as platinum agents, taxanes, 5-fluorouracil, doxorubicin and mitomycin [9][10][11][12].Although the effects of alternative splicing and post-translational glycosylation of CD44 on its interaction with HA have been studied in several tumor types, few data has described the effect of these alterations in LACSCC. The aim of this study is to evaluate the role of CD44 and LeY antigen in the outcome LACSCC patients. Patients and methods Patients:One hundred twenty six women with histologically proven diagnosis of squamous cell carcinoma for uterine cervix, treated at the Abstract Background: Several mechanisms are involved in the development of resistance to therapy in LACSCC. Studies have shown that CD44 and Lewis Y antigen (LeY) form a complex that is associated with chemoresistance, tumor invasion and metastasis. We assessed the role of CD44 and LeY in the outcome of LACSCC patients (pts) treated with different chemotherapy regimens. Methods:A total of 126 LACSCC pts FIGO stages IIB-IVA were selected from GOCS databases: 74 pts included in three different prospective phase II trials in the neoadjuvant setting (vinorelbine, docetaxel, ifosfamide-vinorelbinecisplatin) and 52 pts treated with standard radio-chemotherapy based in cisplatin (RCBC). Clinical data at baseline, disease free survival (DFS) and overall survival (OS) were recorded. Univariate and multivariate Cox models were employed.Results: Median age was 45.6 years (range: 24.9 -80.5). Sixty-three and 47 tumors were CD44+ and LeY+, respectively. Expansive growth tumors showed a higher grade (p=.0024), mitotic index (p=.0505), tumoral necrosis (p=.0191), LeY+ (p=.0034) and CD44+/LeY+ co-expression (p=.0334). CD44+ cells were present in 91.3% of those with local recurrence (p=.0317). Advanced stage was associated with LeY+ tumors (p=.0057). Pts treated with RCBC had worse DFS and OS when their tumors expressed LeY antigen (p=.0083 and p=.0137, respectively). Pre-treatment hemoglobin level, FIGO stage and tumor response remained the most significant prognostic factors in Cox regression. Conclusions:In our cohort of LACSCC pts, the co-expression of CD44+/LeY+ was not associated with worse outcome. However, in the subgroup of pts receiving RCBC, LeY expression was correlated with shorter DFS and OS.

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Alterations in the glycolipid composition and cellular properties of ovarian carcinoma‐derived RMG‐1 cells on transfection of the α1,2‐fucosyltransferase gene

Cited by 50 publications

References 15 publications

Expression of α2,6-sialic acid-containing and Lewis-active glycolipids in several types of human ovarian carcinomas

Expression of α2,6-sialic acid-containing and Lewis-active glycolipids in several types of human ovarian carcinomas

Enhanced expression of unique gangliosides with GM2-determinant in human uterine cervical carcinoma-derived cell lines

Relevant Role of Di-Fucosylated Ley Antigen in the Outcome of Locally Advanced Cervical Squamous Cell Carcinoma Patients Treated with Cisplatin Regimen

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