Claudin 4 Is differentially expressed between ovarian cancer subtypes and plays a role in spheroid formation.
Claudin 4 Is differentially expressed between ovarian cancer subtypes and plays a role in spheroid formation.
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DOI：
10.3390/ijms12021334
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发表时间：
2011-02-22
影响因子：
5.6
通讯作者：
Skubitz AP
中科院分区：
文献类型：
--
作者：
Boylan KL;Misemer B;De Rycke MS;Andersen JD;Harrington KM;Kalloger SE;Gilks CB;Pambuccian SE;Skubitz AP
Claudin 4是一种细胞粘附分子，在卵巢癌和其他上皮癌中经常过表达。在这项研究中，我们试图确定claudin 4的表达是否与卵巢癌患者的预后相关，并可能参与肿瘤的进展。我们研究了卵巢癌组织和细胞系中的claudin 4表达，以及通过组织微阵列（TMAs; n = 500）的免疫组织化学染色，患者腹水中存在的球状体和体外形成的球状体。Claudin 4在近70%的卵巢癌组织中表达，并且在卵巢癌亚型中差异表达，在透明细胞亚型中表达最低。在任何亚型中，claudin 4表达与疾病特异性生存率之间均无相关性。在从患者腹水中获得的多细胞球体中也观察到紧密连接蛋白4表达。使用体外球状体形成测定，我们发现与表达高水平的密蛋白4的对照NIH：OVCAR 5细胞相比，用针对密蛋白4的shRNA处理的NIH：OVCAR 5细胞需要更长的时间来形成致密的球状体。通过FITC-葡聚糖排除验证了用紧密连接蛋白4shRNA处理的NIH：OVCAR 5细胞不能形成致密球状体。这些结果证明了紧密连接蛋白4和紧密连接在球状体形成和完整性中的作用。
Claudin 4 is a cellular adhesion molecule that is frequently overexpressed in ovarian cancer and other epithelial cancers. In this study, we sought to determine whether the expression of claudin 4 is associated with outcome in ovarian cancer patients and may be involved in tumor progression. We examined claudin 4 expression in ovarian cancer tissues and cell lines, as well as by immunohistochemical staining of tissue microarrays (TMAs; n = 500), spheroids present in patients’ ascites, and spheroids formed in vitro. Claudin 4 was expressed in nearly 70% of the ovarian cancer tissues examined and was differentially expressed across ovarian cancer subtypes, with the lowest expression in clear cell subtype. No association was found between claudin 4 expression and disease-specific survival in any subtype. Claudin 4 expression was also observed in multicellular spheroids obtained from patients’ ascites. Using an in vitro spheroid formation assay, we found that NIH:OVCAR5 cells treated with shRNA against claudin 4 required a longer time to form compact spheroids compared to control NIH:OVCAR5 cells that expressed high levels of claudin 4. The inability of the NIH:OVCAR5 cells treated with claudin 4 shRNA to form compact spheroids was verified by FITC-dextran exclusion. These results demonstrate a role for claudin 4 and tight junctions in spheroid formation and integrity.
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影响因子：
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