Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan, R.O.C.
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C.
Int J Oncol. 2018 Feb;52(2):433-440. doi: 10.3892/ijo.2017.4226. Epub 2017 Dec 12.
In the tumor microenvironment, soluble molecules play important role in the establishment of a pre-metastatic niche. The S100 calcium-binding protein family are inflammatory molecules that contribute to the development of a pro-inflammatory tumor microenvironment. S100B belongs to the S100 family and serum S100B (also known as S100beta) serves as a marker for metastasis in lung cancer, ovarian cancer and melanoma. However, the association between S100B and the metastasis of breast cancer is not yet well understood. In the present study, a relatively low S100B expression was observed in the tumor samples compared to normal breast tissue among online microarray datasets. When the estrogen receptor (ER)-negative breast cancer cell lines, MDA-MB-231 and Hs578T, were treated with recombinant human S100B, cell migration was significantly inhibited and epithelial cadherin expression was increased. Our results revealed that a high S100B expression predicted a good overall survival in patients with ER-negative breast cancer, and good distant metastases-free survival in all patients with breast cancer via the analysis of the KM plotter and SurvExpress databases. Although previous studies have indicated that the interaction of S100B with wild-type p53 inhibits p53 function, a high S100B expression is associated with a good prognosis in patients with p53 mutant and p53 wild-type breast cancers. On the whole, our findings demonstrate that S100B treatment suppresses the migratory capacity of ER-negative breast cancer and that S100B expression may serve a predictive marker for metastasis in breast cancer.
在肿瘤微环境中,可溶性分子在建立转移前生态位中发挥重要作用。S100 钙结合蛋白家族是炎性分子,有助于形成促炎肿瘤微环境。S100B 属于 S100 家族,血清 S100B(也称为 S100beta)是肺癌、卵巢癌和黑色素瘤转移的标志物。然而,S100B 与乳腺癌转移之间的关系尚不清楚。在本研究中,与正常乳腺组织相比,在线微阵列数据集的肿瘤样本中 S100B 的表达相对较低。当用重组人 S100B 处理雌激素受体(ER)阴性乳腺癌细胞系 MDA-MB-231 和 Hs578T 时,细胞迁移明显受到抑制,上皮钙黏蛋白表达增加。我们的结果表明,通过对 KM plotter 和 SurvExpress 数据库的分析,高 S100B 表达预测 ER 阴性乳腺癌患者总体生存率良好,所有乳腺癌患者远处无转移生存率良好。尽管先前的研究表明 S100B 与野生型 p53 的相互作用抑制了 p53 功能,但高 S100B 表达与 p53 突变和 p53 野生型乳腺癌患者的良好预后相关。总的来说,我们的研究结果表明,S100B 处理可抑制 ER 阴性乳腺癌的迁移能力,S100B 表达可能成为乳腺癌转移的预测标志物。