Epithelial-mesenchymal transition (EMT) plays a role in tissue repair and pathological processes, notably in tissue fibrosis and facilitates tumor metastasis (12). During EMT, epithelial cancer cells acquire a mesenchymal phenotype and express mesenchymal markers, such as vimentin (13,14). EMT

Abstract

Polysialic acid (PSA) is highly expressed during embryonic development, but barely expressed during postnatal development, and may be ‘re-expressed’ in cancer tissues. In this study, motility and migration assays were performed to compare the changes in cell behavior between non-malignant and maligant cells. Next, the expression levels of PSA were evaluated in 4 human and mouse normal breast or breast cancer (BC) cell lines using 1,2-diamino-4,5-methylenedioxybenzene-labeling HPLC technology, as well as in human clinical BC tissue samples. PSA expression was significantly higher in malignant cells (where it appeared to facilitate cell migration and motility) than in non-malignant cells. Enhanced PSA expression levels were also observed during epithelial-mesenchymal transition (EMT), a leading cause of cancer cell metastasis, which was induced in the NMuMG and MCF10A cells by treatment with transforming growth factor-β1 (TGF-β1). An increased PSA expression also correlated with the disease stage in the patients with BC (P<0.0001). Using RT-qPCR, we found that polysialyltransferase ST8SiaIV (PST) and polysialyltransferase ST8SiaII (STX), which are responsible for PSA synthesis, were differently expressed in the tested BC samples. However, PST, but not STX, was re-expressed in 14 out of 20 clinical BC samples. The findings of the present study indicate that the pathophysiology of BC involves the aberrant regulation of PSA expression and PST gene expression. Introduction Sialic acids, which are mainly attached to the terminal of N-glycans, are abundantly present in a number of organisms, particularly during embryonic development. Sialic acids have been found to mediate various cellular processes in mammals. Polysialic acid (PSA) is a negatively charged homopolymer composed of α-(2,8)-linked sialic acid residues, which is involved in brain development and certain psychiatric disorders, such as schizophrenia (1-3). PSA is barely expressed during postnatal development, but may be ‘re-expressed’ in a number of types of tumor (such as lung cancer, pancreatic cancer, neuroblastoma and glioma), where it modulates cell adhesion, migration and invasion (4-7). The biosynthesis of PSA is catalyzed by two Golgi-resident polysialyltransferases, ST8SiaIV (PST) and ST8SiaII (STX) (8). It has been demonstrated that the mRNA levels of PST and STX are closely associated with the development of pancreatic cancer (9) and non-small cell lung cancer (10). In patients with breast cancer (BC), serum levels of PSA and sialyltransferases have been shown to be positively associated with the presence of malignant tumors and negatively with responses to anticancer treatment (11). However, to the best of our knowledge, few studies to date have examined the expression of PSA and polysialyltransferases in tissues from patients with BC. Epithelial-mesenchymal transition (EMT) plays a role in tissue repair and pathological processes, notably in tissue fibrosis and facilitates tumor metastasis (12). During EMT, epithelial cancer cells acquire a mesenchymal phenotype and express mesenchymal markers, such as vimentin (13,14). EMT is therefore a potential target for the development of novel immunotherapeutic approaches. Sialic acids, the ligands for the sialic-acid-binding immunoglobulin-like lectins (Siglec) family of cell adhesion molecules, appear to be involved in regulating the immune response (15). Exploiting the enzymatic permissiveness of sialic acids has been successfully used for the immunotargeting of cancer cells (16). Thus, PSA may be a useful immunotherapeutic target for cancer cells undergoing EMT. The cell lines, NMuMG and MCF10A, derived respectively from mouse mammary glands and non-malignant human breast epithelial tissues, are commonly used for studies Enhanced expression of polysialic acid correlates with malignant phenotype in breast cancer cell lines and clinical tissue samples XIN WANG1, XIANG LI2, YING-NAN ZENG1, FA HE1, XIAO-MIN YANG3,4 and FENG GUAN1 1Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, 2Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu 214122; 3Department of Surgical Oncology, The First Affiliated Hospital, Medicine School, Xi'an Jiaotong University; 4Center of Breast Oncology, Shaanxi Provincial Tumor Hospital, Xi'an, Shaanxi 710004, P.R. China Received March 6, 2015; Accepted October 16, 2015 DOI: 10.3892/ijmm.2015.2395 Correspondence to: Dr Feng Guan, Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, 1800 Lihu Avenue, Wuxi, Jiangsu

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@inproceedings{Wang2015EpithelialmesenchymalT, title={Epithelial-mesenchymal transition (EMT) plays a role in tissue repair and pathological processes, notably in tissue fibrosis and facilitates tumor metastasis (12). During EMT, epithelial cancer cells acquire a mesenchymal phenotype and express mesenchymal markers, such as vimentin (13,14). EMT}, author={Xin Wang and Xiang Li and Ying Zeng and Fa He and Xiao Yang and Feng Guan}, year={2015} }