Aberrant sialylation is closely associated with the malignant phenotype of cancer cells and metastatic potential. However, the precise nature of the molecules in breast cancers

Aberrant sialylation is closely associated with the malignant phenotype of cancer cells and metastatic potential. However, the precise nature of the molecules in breast cancers has not been unveiled. In this study, we investigated the expression levels of α2,3-sialic acid residues of 50 primary tumor cases, 50 pair-matched lymph node metastasis tumor samples and in the MDA-MB-231, t-47D and McF-7 breast cancer cell lines with different metastatic potential. the expression of α2,3-sialic acid residues was analyzed by histochemistry, cytochemistry and flow cytometry with Maackia amurensis lectin (MAl). the invasion and migration abilities of cells were examined using cell adhesion and transwell in vitro assays. pair-matched lymph node metastasis tumor samples exhibited higher levels of expression of α2,3-sialic acid residues compared to that of primary tumors (p=0.0432). Furthermore, of 38 tumors cases in t1/t2 stages, 31 (81.58%) had weak staining for MAL, which specifically binds to α2,3-sialic acid residues, whereas of 12 tumor cases in t3/t4 stages, only 1 (8.33%) had weak reactions for MAl. the highly metastatic breast cancer cell line MDA-MB-231 exhibited the strongest binding to MAl and the highest expression levels of α2,3-sialic acid residues among the selected cell lines, depending on mrnA expression levels of α2,3-sialyltransferase gene. the adhesion, invasion and migration activities confirmed that MDA-MB-231 exhibited the greater cell adhesion to, migration toward and invasion to Matrigel. taken together, the high expression of α2,3-sialic acid residues in breast cancer was associated with metastatic potential. this property may be important for developing new therapeutic approaches for breast cancer. Introduction Aberrant sialylation is most ubiquitous in malignant tumor cells. sialic acids, as terminal monosaccharide were added to protein or lipid moieties, linked to galb1,3(4)glcnAc/glc via α2,3 or α2,6 and mediated a variety of pathological process. the altered sialic acid residues are closely associated with the malignant phenotype of cancer cells and metastatic potential (1-4). the correlation between sialic acids content and tumor metastatic potential has been reported in many tumors and has received much attention recently. It has been proven that aberrant expression of terminal sialic acids, and in particular α2,3-sialic acids are related to tumor adhesion and invasion (5,6). High levels of sialylation of cell surface glycoconjugates could significantly increase metastasis of colon carcinoma cells and human melanoma cells (7-9). expressions of α2,3sialic acid residues of n-cadherin were altered in metastatic melanoma cell lines (10). this possibility is further supported in the experiment where soyasaponin I significantly impaired metastatic ability of breast cancer by decreasing expression of cell surface α2,3-sialic acids (11). Inhibition expression of α2,3-sialic acid residues may decrease the migratory ability of highly metastatic B16F10 melanoma cells (12). to the best of our knowledge, the precise nature of the molecules has not been fully unveiled nor documented to be of clinical relevance, although the elevated expression of sialylation residues in breast cancer has been reported (13,14). In this study, we investigated the expression of α2,3-sialic acid residues of 50 primary tumor cases, 50 pair-matched lymph node metastasis tumor samples and in three breast cancer cell lines with different metastatic potential (MDAMB-231, T-47D, and MCF-7) using a specific lectin, and the association of invasion and metastasis was analyzed. Materials and methods Tumor samples. tissue samples of 100 patients who underwent surgery were obtained from tissue array (shanxi chaoying Biotechnology co., ltd., china). there were 50 primary tumors and 50 pair-matched lymph node metastasis tumors. Age of the patients ranged from 28 to 80 years with a mean of 50.4 years. Depth of invasion, 10 tumors were staged t1, 28 as t2, 8 as t3, and 4 as t4, based on International Union Against cancer (UIcc) tnM staging system (15). Differential expression of the α2,3-sialic acid residues in breast cancer is associated with metastatic potential HongXIA cUI1,2*, yU lIn1*, lIlIng yUe3, XUeMeI ZHAo1* and JIcHeng lIU3 1Department of pharmacology, Qiqihar Medical college, Qiqihar, Heilongjiang; 2Heilongjiang University of chinese Medicine, Harbin 150040; 3Institute of Medicine, Qiqihar Medical college, Qiqihar, Heilongjiang, p.r. china received november 4, 2010; Accepted January 24, 2011 DoI: 10.3892/or.2011.1192 Correspondence to: Dr Ji-cheng liu, the Institute of Medicine, Qiqihar Medical Univeristy, 333 BuKui street, JianHua District, Qiqihar, Heilongjiang 161042, p.r. china e-mail: [email protected] *contributed equally