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乳腺癌中 α2,3-唾液酸残基的差异表达与转移潜能相关。

Differential expression of the α2,3-sialic acid residues in breast cancer is associated with metastatic potential.

机构信息

Department of Pharmacology, Qiqihar Medical College, Qiqihar, Heilongjiang, PR China.

出版信息

Oncol Rep. 2011 May;25(5):1365-71. doi: 10.3892/or.2011.1192. Epub 2011 Feb 22.

Abstract

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.

摘要

唾液酸化异常与癌细胞的恶性表型和转移潜能密切相关。然而,乳腺癌中具体的分子性质尚未被揭示。在这项研究中,我们研究了 50 例原发性肿瘤病例、50 对配对淋巴结转移肿瘤样本以及具有不同转移潜能的 MDA-MB-231、T-47D 和 MCF-7 乳腺癌细胞系中α2,3-唾液酸残基的表达水平。使用 Maackia amurensis 凝集素(MAL)通过组织化学、细胞化学和流式细胞术分析α2,3-唾液酸残基的表达。使用细胞黏附和 Transwell 体外测定法检测细胞的侵袭和迁移能力。配对的淋巴结转移肿瘤样本的α2,3-唾液酸残基表达水平高于原发性肿瘤(P=0.0432)。此外,在 T1/T2 期的 38 例肿瘤病例中,有 31 例(81.58%)MAL 染色较弱,MAL 特异性结合α2,3-唾液酸残基,而在 T3/T4 期的 12 例肿瘤病例中,只有 1 例(8.33%)MAL 反应较弱。高转移性乳腺癌细胞系 MDA-MB-231 表现出与 MAL 最强的结合以及所选细胞系中最高的α2,3-唾液酸残基表达水平,这取决于α2,3-唾液酰基转移酶基因的 mRNA 表达水平。黏附、侵袭和迁移活性证实 MDA-MB-231 表现出更强的细胞黏附、向 Matrigel 迁移和侵袭能力。综上所述,乳腺癌中α2,3-唾液酸残基的高表达与转移潜能相关。这种特性可能对开发乳腺癌的新治疗方法很重要。

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