-
[show abstract]
[hide abstract]
ABSTRACT: Lewis (y) antigen, a difucosylated oligosaccharide, has been shown to be associated with malignant properties of ovarian carcinomas. In this study, we have investigated the potential role of Lewis (y) antigen, which was stably transfected into ovarian cancer RMG-1 cells, on carboplatin-induced apoptosis. Overexpression of Lewis (y) antigen effectively protected vitronectin-adherent RMG-1 cells from carboplatin-induced apoptosis as assessed by Hoechst 33258 staining and flow cytometry. Treatment with anti-Lewis (y) antigen, anti-integrin αv, or anti-integrin β3 antibody partially abolished the protective effect on apoptosis and markedly inhibited the expression of Topo-II β in cells overexpressing Lewis (y) antigen (all P < 0.01). Moreover, elevated expression of Topo-I and Topo-II β was found in Lewis (y) antigen-overexpressing cells (P < 0.01). However, no obvious changes in Topo-II α were observed throughout the study (P > 0.05). Taken together, these data suggest that the overexpression of Lewis (y) antigen confers cell adhesion-mediated drug resistance to apoptosis in ovarian cancer cells by the upregulation of Topo-I and Topo-II β. Therefore, the inhibition of Lewis (y) antigen may be a novel strategy of cancer chemotherapy.
The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology 06/2011; 294(6):961-9. · 1.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study aimed to measure and correlate the expression of insulin-like growth factor receptor-1 (IGF-1R) and the Lewis(y) antigen in ovarian cancer cell lines and tissue samples.
Reverse transcriptase PCR (RT-PCR), Western blotting, immunoprecipitation, immunohistochemistry, and immunofluorescence double-labeling techniques were applied to detect and measure the expression of Lewis(y) and IGF-1R.
In α1,2-fucosyltransferase (α1,2-FT)-transfected cells, IGF-1R expression was significantly upregulated compared with cells that do not overexpress α1,2-FT (P < 0.05). The amount of Lewis(y) expressed on IGF-1R increased 1.81-fold in α1,2-FT-overexpressing cells (P < 0.05), but the ratio of Lewis(y) expressed on IGF-1R to total IGF-1R was unaltered between two cells (P > 0.05). In malignant epithelial ovarian tumors, the positivity rates of Lewis(y) and IGF-1R detection were 88.3% and 93.33%, respectively, which is higher than the positivity rates in marginal (60.00% and 63.33%, all P < 0.05), benign (33.00% and 53.33%, all P < 0.01), and normal (0% and 40%, all P < 0.01) ovarian samples. No correlations were detected in positivity rates of Lewis(y) or IGF-1R expression with respect to clinicopathological parameters in ovarian cancers (all P > 0.05). Both IGF-1R and Lewis(y) were highly expressed in ovarian cancer tissues, and their expression levels were positively correlated (P < 0.05).
Overexpression of Lewis(y) results in overexpression of IGF-1R. Both IGF-1R and Lewis(y) are associated with the occurrence and development of ovarian cancers.
International Journal of Molecular Sciences 01/2011; 12(10):6781-95. · 2.60 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To detect the expression and clinical significances of Lewis y antigen and integrin αv, β3 in epithelial ovarian tumors, and to explore the expression correlation between Lewis y antigen and integrin αv, β3.
Immunohistochemical staining was performed in 95 cases of epithelial ovarian cancer, 37 cases of borderline tumors, 20 cases of benign tumors, and 20 cases of normal ovarian tissue, for the detection of Lewis y antigen and integrin αv, β3 expressions, and to analyze the relationship between Lewis y antigen and integrin, and the relationship between clinical and pathological parameters of ovarian cancer. In addition, immunofluorescence double labeling was utilized to detect the expression correlation between Lewis y antigen and integrin αv, β3 in ovarian cancer.
In epithelial ovarian tumors, the expression rate of Lewis y antigen was 81.05%, significantly higher than that of borderline (51.53%) (P < 0.05) and benign (25%) (P < 0.01) tumors, and normal ovarian tissues (0) (P < 0.01). The expression rate of integrin αv, β3 in malignant epithelial ovarian tumors was 78.95% and 82.11%, respectively, significantly higher than that of the borderline (45.94%, 40.54%) (both P < 0.05), benign group (10.00%, 15.00%) (both P < 0.01) and normal ovary group (5%, 15%) (both P < 0.01).
Lewis y and integrins αv, β3 are relevant to pelvic and abdominal diffusion and metastasis of ovarian cancer cells, suggesting that these two molecules mediate a boosting function for tumor metastasis.
International Journal of Molecular Sciences 01/2011; 12(6):3409-21. · 2.60 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study investigates the expression and the clinical significance of Lewis y and integrins α5 and β1 in serous and mucinous ovarian tumors and then evaluates the association between them.
Lewis y and integrin α5 and β1 expression are detected on tissues from malignant, borderline, and benign ovarian serous and mucinous tumors and normal tissues. Their expression and relationship are assessed in paraffin sections using immunohistochemistry and double-labeling immunofluorescence method.
Lewis y was mainly expressed in ovarian serous and mucinous cancers (88.33%); its positive rate was obviously higher than rates in the borderline (60.00%, P < 0.05) and benign ovarian tumors (35.00%, P < 0.01) and normal ovarian tissues (0, P < 0.01) and was not associated with clinicopathological characteristics. Integrins α5 (85.00%) and β1 (81.67%) were also mainly expressed in ovarian serous and mucinous cancers; their positive rates were all obviously higher than those in benign ovarian tumors (60.00% and 55.00%, respectively; all P < 0.05) and normal tissues (40.00% and 30.00%, respectively; all P < 0.01). Increased expression of integrins α5 and β1 correlated with higher clinical stage (P < 0.05) but were not associated with histological types, differentiation degree, and lymphatic metastasis (P > 0.05). The expression intensity of Lewis y and integrins α5 and β1 was significant with clinical stage and differentiation degree (all P < 0.05) in ovarian cancer; positive significant correlation between Lewis y antigen and integrins α5 and β1 was observed in serous and mucinous ovarian cancer tissues.
A close correlation between Lewis y, integrins α5 and β1, and ovarian cancer was observed. Lewis y can influence the biological behavior of a tumor cell as an important composition of integrins α5 and β1 by some signal pathway, such as promoting cell adhesion and migration, and this study provides theoretical evidence of ovarian cancer biological treatment.
International Journal of Gynecological Cancer 12/2010; 20(9):1482-9. · 1.65 Impact Factor
-
[show abstract]
[hide abstract]
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.
International Journal of Molecular Sciences 01/2010; 11(11):4441-52. · 2.60 Impact Factor
