High Expression of Lewis y Antigen and CD44 Is Correlated with Resistance to Chemotherapy in Epithelial Ovarian Cancers
et al. (2013) High Expression of Lewis y Antigen and CD44 Is Correlated with Resistance to Chemotherapy in
Epithelial Ovarian Cancers. PLoS ONE 8(2): e57250. doi:10.1371/journal.pone.0057250
High Expression of Lewis y Antigen and CD44 Is Correlated with Resistance to Chemotherapy in Epithelial Ovarian Cancers
Zhenhua Hu 0 1
Jian Gao 0 1
Danye Zhang 0 1
Qing Liu 0 1
Limei Yan 0 1
Lili Gao 0 1
Juanjuan Liu 0 1
Dawo Liu 0 1
Shulan Zhang 0 1
Bei Lin 0 1
Shannon M. Hawkins, Baylor College of Medicine, United States of America
0 Current address: Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University , Shenyang, Liaoning Province , China
1 Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University , Shenyang, Liaoning Province , China
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.
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Funding: This work is supported by the National Natural Science Foundation of China (No. 30872757, 81072118, 81172491, 81101527); Ph.D. Programs
Foundation of Ministry of Education of China (No. 20112104110016, 20112104120019); Science Committee Foundation of Shenyang City, China (No.
F10-14-9-952); Shengjing Free Researcher Project (No. 200807). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of
the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
Development of resistance to chemotherapy in epithelial
ovarian cancers involves multiple mechanisms. In recent years,
cell adhesion-mediated drug resistance (CAM-DR) has become an
active area of investigation in the study of tumor drug resistance.
For example, the hyaluronan (HA)-specific receptor, CD44, which
plays an important role in adhesion, has been shown to be
involved in CAM-DR through interactions with its ligand HA
[1,2]. Several studies have revealed that CD44s is highly expressed
in situ and metastatic ovarian cancers and that CD44 expression is
correlated with malignant behaviors of ovarian cancer cells, such
as adhesion, invasion, and metastasis [3,4]. CD44 is modified
posttranslationally by glycosylation, which has been shown to influence
CD44-mediated CAM-DR [5]. In our preliminary studies, we
have found that, although CD44 mRNA levels were similar in
a1,2-fucosyltransferase transfected ovarian cancer cells
(RMG-1H) and the parent cells (RMG-1), CD44 protein expression levels
were significantly higher in the RMG-1-H cells. In addition, we
found that the di-fucosylated Lewis y antigen was a part of the
composition of CD44 and that increased expression of this antigen
correlated with increased CD44-mediated ovarian cell adhesion
and migration [6]. Increased expression of Lewis y antigen and
CD44 in RMG-1-H cells was associated with increased resistance
to chemotherapeutic drugs, including 5-fluorouracil, carboplatin
and paclitaxel (TaxolH) [7,8]. Although the effects of alternative
splicing and post-translational glycosylation of CD44 on its
interaction with HA have been widely studied in recent years,
few reports have described the effects of alterations in fucosylation
on CD44-dependent CAM-DR of ovarian cancer cells. Therefore,
to address this question, in the present study, we have quantified
ovarian cancer drug resistance and expression of Lewis y antigen
and CD44 in tissues from ovarian cancer patients. We then used
these data to investigate correlations between expression of Lewis y
antigen and CD44 and chemotherapeutic resistance, in addition to
assess the clinical significance of these correlations.
Materials and Methods
This study was approved by the Institutional Review Board of
Shengjing Hospital. Between May 2005 and July 2009, 92 Chinese
patients diagnosed with primary epithelial ovarian cancer by
surgery and pathological analysis were retrospectively identified
from the records of Shengjing Hospital Affiliated to China
Medical University. All patients underwent treatment for ovarian
cancer that included surgical debulking, followed by 68
postoperative cycles of paclitaxel (TaxolH) plus carboplatin (TC
regimen) conventional chemotherapy. The chemotherapy
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