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Lewis Y Promotes Growth and Adhesion of Ovarian Carcinoma-Derived RMG-I Cells by Upregulating Growth Factors  [PDF]
Feifei Li,Bei Lin,Yingying Hao,Yan Li,Juanjuan Liu,Jianping Cong,Liancheng Zhu,Qing Liu,Shulan Zhang
International Journal of Molecular Sciences , 2010, DOI: 10.3390/ijms11103748
Abstract: Lewis y (LeY) antigen is a difucosylated oligosaccharide carried by glycoconjugates on the cell surface. Overexpression of LeY is frequently observed in epithelial-derived cancers and has been correlated to the pathological staging and prognosis. However, the effects of LeY on ovarian cancer are not yet clear. Previously, we transfected the ovarian cancer cell line RMG-I with the α1,2-fucosyltransferase gene to obtain stable transfectants, RMG-I-H, that highly express LeY. In the present study, we examined the proliferation, tumorigenesis, adhesion and invasion of the cell lines with treatment of LeY monoclonal antibody (mAb). Additionally, we examined the expression of TGF-β1, VEGF and b-FGF in xenograft tumors. The results showed that the proliferation and adhesion in vitro were significantly inhibited by treatment of RMG-I-H cells with LeY mAb. When subcutaneously inoculated in nude mice, RMG-I-H cells produced large tumors, while mock-transfected cells RMG-I-C and the parental cells RMG-I produced small tumors. Moreover, the tumor formation by RMG-I-H cells was inhibited by preincubating the cells with LeY mAb. Notably, the expression of TGF-β1, VEGF and b-FGF all increased in RMG-I-H cells. In conclusion, LeY plays an important role in promoting cell proliferation, tumorigenecity and adhesion, and these effects may be related to increased levels of growth factors. The LeY antibody shows potential application in the treatment of LeY-positive tumors.
High Expression of Lewis y Antigen and CD44 Is Correlated with Resistance to Chemotherapy in Epithelial Ovarian Cancers  [PDF]
Zhenhua Hu, Jian Gao, Danye Zhang, Qing Liu, Limei Yan, Lili Gao, Juanjuan Liu, Dawo Liu, Shulan Zhang, Bei Lin
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0057250
Abstract: Objectives To measure Lewis y antigen and CD44 antigen expression in epithelial ovarian carcinoma and to correlate the levels of these antigens with clinical response to chemotherapy. Methods The study cases included 34 cases of ovarian carcinoma with resistance to chemotherapeutic drugs, 6 partially drug-sensitive cases, and 52 drug-sensitive cases (92 total). Results The rates of expression of Lewis y antigen and CD44 antigen were significantly greater in the drug-resistant group than that in the partially-sensitive or sensitive groups. Surgical stage, residual tumor size and expression of CD44 and Lewis y antigen in ovarian carcinoma tissues were independent risk factors for chemotherapeutic drug resistance. Conclusions Over-expression of Lewis y and CD44 antigen are strong risk factors for chemotherapeutic drug resistance in ovarian carcinoma patients.
Lewis y antigen promotes the proliferation of ovarian carcinoma-derived RMG-I cells through the PI3K/Akt signaling pathway
Juanjuan Liu, Bei Lin, Yingying Hao, Yue Qi, Liancheng Zhu, Feifei Li, Dawo Liu, Jianping Cong, Shulan Zhang, Masao Iwamori
Journal of Experimental & Clinical Cancer Research , 2009, DOI: 10.1186/1756-9966-28-154
Abstract: We constructed a plasmid encoding α1,2-fucosyltransferase (α1,2-FT) gene and then transfected it into ovarian carcinoma-derived RMG-I cells with lowest Lewis y antigen expression level. Effect of Lewis y on cell proliferation was assessed after transfection. Changes in cell survival and signal transduction were evaluated after α-L-fucosidase, anti-Lewis y antibody and phosphatidylinositol 3-kinase (PI3K) inhibitor treatment.Our results showed that the levels of α1,2-FT gene and Lewis y increased significantly after transfection. The cell proliferation of ovarian carcinoma-derived RMG-I cells sped up as the Lewis y antigen was increased. Both of α-L-fucosidase and anti-Lewis y antibody inhibited the cell proliferation. The phosphorylation level of Akt was apparently elevated in Lewis y-overexpressing cells and the inhibitor of PI3K, LY294002, dramatically inhibited the growth of Lewis y-overexpressing cells. In addition, the phosphorylation intensity and difference in phosphorylation intensity between cells with different expression of α1,2-FT were attenuated significantly by the monoantibody to Lewis y and by the PI3K inhibitor LY294002.Increased expression of Lewis y antigen plays an important role in promoting cell proliferation through activating PI3K/Akt signaling pathway in ovarian carcinoma-derived RMG-I cells. Inhibition of Lewis y expression may provide a new therapeutic approach for Lewis y positive ovarian cancer.Lewis y antigen is carried by glycoconjugates (glycoproteins and glycolipids) at cell surface. It is an oligosaccharide with two fucoses, and its chemical structure is Fucα1 → 2Galβ1 → 4 [Fucα1 → 3]GlcNAcβ1 → R, belonging to the A, B, H, Lewis blood group antigens family with specific fucosylation of the terminal end of carbohydrate structure catalyzed by the α1,2-fucosyltransferase [1,2]. The expression of Lewis y antigen primarily occurs during the embryogenesis period. Under physiologic conditions, its expression in adults is limited on the sur
Increase in Docetaxel-Resistance of Ovarian Carcinoma-Derived RMG-1 Cells with Enhanced Expression of Lewis Y Antigen  [PDF]
Fan Zhang,Juanjuan Liu,Bei Lin,Qing Liu,Yue Zhao,Liancheng Zhu,Yingying Hao,Shulan Zhang,Masao Iwamori
International Journal of Molecular Sciences , 2011, DOI: 10.3390/ijms12117323
Abstract: Epithelial carcinomas of the ovary exhibit the highest mortality rate among gynecologic malignancies. Studies found that the metabolism of glycolipids or carbohydrates is associated with acquirement of anticancer drug-resistance by cancer cells. This study was to characterize possible involvement of Lewis Y (Le Y) antigen in the drug-resistance of cancer cells. We transfected the α1,2-fucosyltransferase gene into human ovarian carcinoma-derived RMG-1 cells and established RMG-1-hFUT cells with enhanced expression of Le Y. We determined the effects of docetaxel on the survival of cells by MTT assaying and observed the apoptosis of cells in the presence of docetaxel by flow cytometric analysis and by transmission electron microscopy. Plasma membranes and intracellular granules in RMG-1-hFUT cells were stained with anti-Le Y antibody, the intensity of the staining was higher than that in control cells. The RMG-1-hFUT cells exhibited higher resistance to docetaxel than the control cells with regard to the docetaxel concentration and time course. After treatment with 10 μg/mL docetaxel for 72 h, the control cells, but not RMG-1-hFUT, contained abundant positively stained cell debris due to disintegration of the cytoskeleton. On transmission electron microscopy, although the control cells treated with docetaxel as above showed the following morphology, i.e., absence of villi, cells shrunken in size, pyknosis, agglutinated chromatin and cell buds containing nuclei in the process of apoptosis, the RMG-1-hFUT cells showed only agglutinated chromatin and vacuoles in the cytoplasm. In summary, cells with enhanced expression of Le Y were shown to acquire docetaxel-resistance, indicating the possible involvement of glycoconjugates in the drug-resistance.
卵巢癌细胞系rmg-ⅰlewis(y)抗原含量变化对其卡铂耐药性的影响  [PDF]
赵越?,林蓓?,郝莹莹?,严丽梅?,刘娟娟?,朱连成?,张淑兰?
生物化学与生物物理进展 , 2008,
Abstract: 利用lewis(y)抗原稳定高表达细胞株rmg-ⅰ-h,研究细胞表面lewis(y)抗原含量变化与细胞对卡铂耐药性的关系.利用四甲基偶氮唑盐(mtt)法测定不同浓度卡铂作用后细胞系rmg-ⅰ-h及其对照组rmg-ⅰ、rmg-ⅰ-c的细胞生长抑制率(ir);利用流式细胞仪(fcm)分析细胞凋亡,同时检测药物作用后细胞的凋亡比率;利用荧光染色法和透射电镜进一步观察细胞凋亡状态.结果表明,rmg-ⅰ-h的半数抑制浓度(ic50)为(58.07±2.42),明显高于对照组rmg-ⅰ(28.83±3.57)和rmg-ⅰ-c(25.71±8.24)的ic50(p<0.01),后两者间无统计学差异(p>0.05),流式细胞仪分析证实3组细胞均存在凋亡,经30mg/l、60mg/l卡铂处理后细胞再进行流式细胞仪检测,rmg-ⅰ-h的相对凋亡率分别为(20.43±0.71)%和(38.11±0.33)%,为对照组的49%~63%,明显低于对照组(p<0.05),2个对照组间比较无统计学差异(p>0.05),荧光染色和透射电镜直接观察了细胞形态变化,每个浓度组rmg-ⅰ-h的凋亡程度均低于rmg-ⅰ和rmg-ⅰ-c.说明细胞表面lewis(y)抗原含量增加的同时,卵巢癌细胞对卡铂的耐药性增强.
Lewis (y) Antigen Overexpression Increases the Expression of MMP-2 and MMP-9 and Invasion of Human Ovarian Cancer Cells  [PDF]
Limei Yan,Bei Lin,Lili Gao,Song Gao,Chuan Liu,Changzhi Wang,Yifei Wang,Shulan Zhang,Masao Iwamori
International Journal of Molecular Sciences , 2010, DOI: 10.3390/ijms11114441
Abstract: Lewis (y) antigen is a difucosylated oligosaccharide present on the plasma membrane, and its overexpression is frequently found in human cancers and has been shown to be associated with poor prognosis. Our previous studies have shown that Lewis (y) antigen plays a positive role in the process of invasion and metastasis of ovarian cancer cells. However, the mechanisms by which Lewis (y) antigen enhances the invasion and tumor metastasis are still unknown. In this study, we established a stable cell line constitutively expressing Lewis (y) antigen (RMG-1-hFUT) by transfecting the cDNA encoding part of the human α1,2-fucosyltransferase (α1,2-FUT) gene into the ovarian cancer cell line RMG-1, and investigated whether Lewis (y) antigen regulates the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, and tissue inhibitors of metalloproteinases (TIMP-1) and TIMP-2. We found that RMG-1-hFUT cells exhibited higher invasive capacities than their control cells. In addition, expression of TIMP-1 and TIMP-2 was down-regulated and expression of MMP-2 and MMP-9 was up-regulated. Anti-Lewis (y) antigen antibody treatment significantly reversed the expression of TIMP-1, TIMP-2, MMP-2 and MMP-9. Taken together, we provide the first evidence that down-regulation of TIMP-1 and TIMP-2 and up-regulation of MMP-2 and MMP-9 represents one of the mechanisms by which Lewis (y) antigen promotes cell invasion.
Lewis y Regulate Cell Cycle Related Factors in Ovarian Carcinoma Cell RMG-I in Vitro via ERK and Akt Signaling Pathways  [PDF]
Dawo Liu,Juanjuan Liu,Bei Lin,Shuice Liu,Rui Hou,Yingying Hao,Qing Liu,Shulan Zhang,Masao Iwamori
International Journal of Molecular Sciences , 2012, DOI: 10.3390/ijms13010828
Abstract: Objective: To investigate the effect of Lewis y overexpression on the expression of proliferation-related factors in ovarian cancer cells. Methods: mRNA levels of cyclins, CDKs, and CKIs were measured in cells before and after transfection with the α1,2-fucosyltransferase gene by real-time PCR, and protein levels of cyclins, CDKs and CKIs were determined in cells before and after gene transfection by Western blot. Results: Lewis y overexpression led to an increase in both mRNA and protein expression levels of cyclin A, cyclin D1 and cyclin E in ovarian cancer cells, decrease in both mRNA and protein expression levels of p16 and p21, and decrease of p27 at only the protein expression level without change in its mRNA level. There were no differences in proteins and the mRNA levels of CDK2, CDK4 and CDK6 before and after gene transfection. Anti-Lewis y antibody, ERK and PI3K pathway inhibitors PD98059 and LY294002 reduced the difference in cyclin and CKI expression caused by Lewis y overexpression. Conclusion: Lewis y regulates the expression of cell cycle-related factors through ERK/MAPK and PI3K/Akt signaling pathways to promote cell proliferation.
Role of Versican, Hyaluronan and CD44 in Ovarian Cancer Metastasis  [PDF]
Miranda P. Ween,Martin K. Oehler,Carmela Ricciardelli
International Journal of Molecular Sciences , 2011, DOI: 10.3390/ijms12021009
Abstract: There is increasing evidence to suggest that extracellular matrix (ECM) components play an active role in tumor progression and are an important determinant for the growth and progression of solid tumors. Tumor cells interfere with the normal programming of ECM biosynthesis and can extensively modify the structure and composition of the matrix. In ovarian cancer alterations in the extracellular environment are critical for tumor initiation and progression and intra-peritoneal dissemination. ECM molecules including versican and hyaluronan (HA) which interacts with the HA receptor, CD44, have been shown to play critical roles in ovarian cancer metastasis. This review focuses on versican, HA, and CD44 and their potential as therapeutic targets for ovarian?cancer.
On the parameters of Lewis metric for the Lewis class  [PDF]
M. F. A. da Silva,L. Herrera,F. M. Paiva,N. O. Santos
Physics , 1996, DOI: 10.1088/0264-9381/12/1/009
Abstract: The physical and geometrical meaning of the four parameters of Lewis metric for the Lewis class are investigated. Matching this spacetime to a completely anisotropic, rigidly rotating, fluid cylinder, we obtain from the junction conditions that the four parameters are related to the vorticity of the source. Furthermore it is shown that one of the parameters must vanish if one wishes to reduce the Lewis class to a locally static spacetime. Using the Cartan scalars it is shown that the Lewis class does not include globally Minkowski as special class, and that it is not locally equivalent to the Levi-Civita metric. Also it is shown that, in contrast with the Weyl class, the parameter responsible for the vorticity appears explicitly in the expression for the Cartan scalars. Finally, to enhance our understanding of the Lewis class, we analyse the van Stockum metric.
Recent Unrest in the RMG Sector of Bangladesh: Is this an Outcome of Poor Labour Practices?  [cached]
Chowdhury Golam Hossan,Md. Atiqur Rahman Sarker,Rumana Afroze
International Journal of Business and Management , 2012, DOI: 10.5539/ijbm.v7n3p206
Abstract: The RMG sector of Bangladesh has experienced disputes and violent protest by the workers in recent times. This study explores the reasons for recent unrest in the garment sector. Since managers are mainly responsible for applying human resource practices, this paper has given particular attention to their views on recent attitude changes of workers. Results show that mutual understanding among workers and managers is absent in the RMG sector. This study also states that high-work load, poor behaviour of line managers, low skills and low wage rates are the notable reasons for high job turnover and social unrest. Poor relationship between workers and supervisors is the main source of conflict. This study finds that there is growing demand for work life balance among the workers of RMG sector.
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