Lewis (y) Antigen Overexpression Increases the Expression of MMP-2 and MMP-9 and Invasion of Human Ovarian Cancer Cells

Yan, Limei; Lin, Bei; Gao, Lili; Gao, Song; Liu, Chuan; Wang, Changzhi; Wang, Yifei; Zhang, Shulan; Iwamori, Masao

doi:10.3390/ijms11114441

Cited by 47 publications

(31 citation statements)

References 21 publications

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“…Cervical tumors that extended to pelvic wall or compromised the vagina, bladder or rectum, or extended beyond true pelvis (FIGO stages III-IV) were associated to a significant increase of LeY expression in our study. Overexpression of LeY antigen could be responsible for an up-regulation of matrix metalloproteinases (MMPs), which lead to breakdown the extracellular matrix (ECM), and a down-regulation of specific tissue inhibitors of metalloproteinases (TIMPs) promoting the process of invasion although the specific mechanism still need to be further studied [26].…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…Increased expression promotes EMT transition and metastasis in breast cancer Role in synthesising the F77 antigen which increases prostate cancer cell growth FUT1 O-fucosyltransferase important for the biosynthesis of H antigens, Lewis B, and Lewis Y Linked to prognosis in breast cancer (Milde-Langosch et al 2014). Acts as an oncogene in several cancer types (Hao et al 2008, Yan et al 2010 Role in synthesising the F77 antigen which increases prostate cancer cell growth Hexosamine biosynthetic pathway (HBP) UAP1 Final enzyme in the hexosamine biosynthetic pathway (HBP)…”

Section: :3mentioning

confidence: 99%

“…Although GCNT2 is not well studied in prostate cancer, increased GCNT2 has been shown to promote an epithelial-to-mesenchymal transition (EMT) and metastasis in breast cancer cells . Similarly, the fucosyltransferase FUT1 is also androgen regulated in prostate cancer cells and can act as an oncogene in several cancer types (Hao et al 2008, Yan et al 2010, MildeLangosch et al 2014. GCNT1, GCNT2 and FUT1 are believed to play a role in synthesising the prostate cancerassociated F77 antigen .…”

Section: :3mentioning

confidence: 99%

Glycosylation is a global target for androgen control in prostate cancer cells

Munkley¹

2017

Endocrine-Related Cancer

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Changes in glycan composition are common in cancer and can play important roles in all of the recognised hallmarks of cancer. We recently identified glycosylation as a global target for androgen control in prostate cancer cells and further defined a set of 8 glycosylation enzymes (GALNT7, ST6GalNAc1, GCNT1, UAP1, PGM3, CSGALNACT1, ST6GAL1 and EDEM3), which are also significantly upregulated in prostate cancer tissue. These 8 enzymes are under direct control of the androgen receptor (AR) and are linked to the synthesis of important cancer-associated glycans such as sialyl-Tn (sTn), sialyl LewisX (SLeX), O-GlcNAc and chondroitin sulfate. Glycosylation has a key role in many important biological processes in cancer including cell adhesion, migration, interactions with the cell matrix, immune surveillance, cell signalling and cellular metabolism. Our results suggest that alterations in patterns of glycosylation via androgen control might modify some or all of these processes in prostate cancer. The prostate is an abundant secretor of glycoproteins of all types, and alterations in glycans are, therefore, attractive as potential biomarkers and therapeutic targets. Emerging data on these often overlooked glycan modifications have the potential to improve risk stratification and therapeutic strategies in patients with prostate cancer.

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“…Their ability to contribute to disease pathogenesis by a variety of mechanisms is well-documented (Bafna et al, 2010;Thériault et al, 2011). Increased Le y antigens have been correlated with a number of tumorigenic effects, such as enhanced binding to mesothelial CD44, stimulation of 5 1 signaling, increased expression of MMP-2/9, and down-regulation of inhibitory TIMP-1/2 (Gao et al, 2011;Li et al, 2010b;Yan et al, 2010). A positive effect on growth factor activation has additionally been observed, as Le Y participates in EGFR signaling and aids in the secretion of the angiogenic factors VEGF and basic FGF (Basu et al, 1987;Li et al, 2010b).…”

Section: Fucosylationmentioning

confidence: 99%