Kagara Naofumi, Tanaka Natsumi, Noguchi Shinzaburo, Hirano Toshio
Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences, and Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Cancer Sci. 2007 May;98(5):692-7. doi: 10.1111/j.1349-7006.2007.00446.x. Epub 2007 Mar 14.
Zinc is an essential element, necessary for sustaining all life. Zinc deficiency causes taste impairments, immune deficiency, skin problems, and growth and mental retardation. Recent reports suggest that zinc is associated with an increased risk of cancer, although it is still unclear whether zinc or its transporters are involved in cancer progression. Here we show that zinc and its transporter ZIP10 are involved in the invasive behavior of breast cancer cells. The screening of clinical samples for ZIP10 mRNA expression suggested that ZIP10 was significantly associated with the metastasis of breast cancer to the lymph node. In addition, the expression of ZIP10 mRNA was higher in the invasive and metastatic breast cancer cell lines MDA-MB-231 and MDA-MB-435S than in less metastatic breast cancer cell lines, such as MCF7, T47D, ZR75-1 and ZR75-30. In in vitro cell migration assays, the depletion of zinc transporter ZIP10 and intracellular zinc inhibited the migratory activity of MDA-MB-231 and MDA-MB-435S cells. These results showed that zinc and ZIP10 play an essential role in the migratory activity of highly metastatic breast cancer cells, and suggest ZIP10 as a possible marker for the metastatic phenotype of breast cancer and a promising target of novel treatment strategies.
锌是维持所有生命所必需的元素。锌缺乏会导致味觉障碍、免疫缺陷、皮肤问题以及生长和智力发育迟缓。最近的报告表明锌与癌症风险增加有关,尽管锌及其转运蛋白是否参与癌症进展仍不清楚。在此我们表明锌及其转运蛋白ZIP10参与乳腺癌细胞的侵袭行为。对临床样本进行ZIP10 mRNA表达筛查表明,ZIP10与乳腺癌向淋巴结转移显著相关。此外,ZIP10 mRNA在侵袭性和转移性乳腺癌细胞系MDA-MB-231和MDA-MB-435S中的表达高于转移性较低的乳腺癌细胞系,如MCF7、T47D、ZR75-1和ZR75-30。在体外细胞迁移试验中,锌转运蛋白ZIP10和细胞内锌的缺失抑制了MDA-MB-231和MDA-MB-435S细胞的迁移活性。这些结果表明锌和ZIP10在高转移性乳腺癌细胞的迁移活性中起重要作用,并提示ZIP10可能作为乳腺癌转移表型的标志物以及新型治疗策略的有前景的靶点。