Nuclear expression of S100A4 is associated with aggressive behavior of epithelial ovarian carcinoma: An important autocrine/paracrine factor in tumor progression
Nuclear expression of S100A4 is associated with aggressive behavior of epithelial ovarian carcinoma: An important autocrine/paracrine factor in tumor progression
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DOI：
10.1111/j.1349-7006.2006.00295.x
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发表时间：
2006-10-01
期刊：
影响因子：
5.7
通讯作者：
Konishi, Ikuo
中科院分区：
文献类型：
--
作者：
Kikuchi, Norihiko;Horiuchi, Akiko;Konishi, Ikuo
虽然S100 A4的表达与多种恶性肿瘤的转移有关，但其在卵巢癌中的生物学意义却知之甚少。在这项研究中，我们研究了S100 A4在卵巢癌细胞中的表达和分泌及其细胞外功能。我们首先使用免疫组织化学方法检测了113例上皮性卵巢肿瘤（24例良性，20例交界性和69例恶性肿瘤）中S100 A4的表达和定位，并分析了其在卵巢癌患者中的预后意义。然后我们研究了S100 A4在四种卵巢癌细胞系中的表达、亚细胞定位和分泌。最后，我们检测了S100 A4处理对卵巢癌细胞的细胞增殖和侵袭力的影响，沿着小G T β，RhoA的活化。S100 A4在癌组织中的胞浆和胞核表达均明显强于良性和交界性肿瘤。卵巢癌细胞核S100 A4强表达者生存期明显短于无S100 A4表达者（P = 0.0045）。这不是胞质S100 A4表达的情况。卵巢癌细胞系显示表达S100 A4，并将S100 A4分泌到培养基中。重组S100 A4处理导致S100 A4表达上调，S100 A4易位到细胞核中，并且侵袭性增强，这与小GT3，RhoA的上调有关。提示S100 A4的核表达与卵巢癌的侵袭性有关，S100 A4是一种自分泌/旁分泌因子，在卵巢癌细胞的侵袭性中起重要作用。
Although S100A4 expression has reportedly been associated with metastasis of various malignancies, little is known about its biological significance in ovarian carcinomas. In this study, we investigated expression and secretion of S100A4 and its extracellular function in ovarian carcinoma cells. We first used immunohistochemistry to examine the expression and localization of S100A4 in 113 epithelial ovarian neoplasms (24 benign, 20 borderline, and 69 malignant tumors) and analyzed its prognostic significance in patients with ovarian carcinoma. Then we investigated the expression, subcellular localization, and secretion of S100A4 in four ovarian carcinoma cell lines. Finally, we examined the effect of S100A4 treatment on the cell proliferation and invasiveness of ovarian carcinoma cells, along with activation of small GTPase, RhoA. Both cytoplasmic and nuclear expressions of S100A4 were significantly stronger in carcinomas than those in benign and borderline tumors. Ovarian carcinoma patients with strong nuclear S100A4 expression showed a significantly shorter survival than those without (P = 0.0045). This was not the case for cytoplasmic S100A4 expression. Ovarian carcinoma cell lines were shown to express S100A4, and secrete S100A4 into the culture media. Treatment with recombinant S100A4 resulted in the upregulation of S100A4 expression, translocation of S100A4 into the nucleus, and enhancement of invasiveness, which was associated with the upregulation of small GTPase, RhoA. These findings suggest that the nuclear expression of S100A4 is involved in the aggressive behavior of ovarian carcinoma and S100A4 is an autocrine/paracrine factor that plays an important role in the aggressiveness of ovarian carcinoma cells.