Stanniocalcin 2 promotes invasion and is associated with metastatic stages in neuroblastoma
Stanniocalcin 2 promotes invasion and is associated with metastatic stages in neuroblastoma
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DOI：
10.1002/ijc.24564
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发表时间：
2009-11-01
影响因子：
6.4
通讯作者：
Becker, Juergen
中科院分区：
文献类型：
--
作者：
Volland, Sonja;Kugler, Wilfried;Becker, Juergen
斯钙素2（Stanniocalcin 2，STC 2）是一种分泌型糖蛋白，其功能尚不清楚。我们研究了STC 2在人类神经母细胞瘤，最常见的固体颅外肿瘤的婴儿。在原发性肿瘤样品中，我们发现STC 2的表达与转移性4期和4s期以及MYCN表达相关。然而，在体外，我们证明，细胞增殖减少STC 2由于增加的基础凋亡率的转染细胞。另一方面，体外实验表明，STC 2转染的神经母细胞瘤细胞具有增加的侵袭潜力，并显示出更高的胶原降解基质金属蛋白酶2（MMP 2）活性。使用鸡胚绒毛尿囊膜（CAM）上的实验性肿瘤，我们观察到STC 2表达细胞显示出从实体瘤移出的迹象并破坏CAM的血管，从而引起大量出血的肿瘤。当将纯化的STC 2蛋白应用于CAM时，还观察到血管侵蚀。总之，我们证明了STC 2在神经母细胞瘤中的双重作用。它在体外减少肿瘤细胞的增殖，但增加侵袭潜力并诱导出血，从而可能促进早期转移。STC 2作为转移性神经母细胞瘤的替代标志物的潜力需要进一步研究。(C)2009年UICC
Stanniocalcin 2 (STC2) is a secreted glycoprotein of as yet unknown functions. We investigated STC2 in human neuroblastoma, the most common solid extra-cranial tumor of infancy. In primary tumor samples, we found that expression of STC2 is associated with the metastatic Stages 4 and 4s and MYCN expression. In vitro, however, we demonstrate that cell proliferation is reduced by STC2 due to an increase in the basal apoptosis rate of the transfected cells. On the other hand, in vitro assays showed that STC2-transfected neuroblastoma cells have an increased invasive potential and display higher activity of collagen-degrading matrix metalloproteinase 2 (MMP2). Using experimental tumors on the chick chorioallantoic membrane (CAM), we observed that STC2 expressing cells show signs of emigration from the solid tumor and destroy blood vessels of the CAM, giving rise to massively bleeding tumors. Erosion of blood vessels was also seen when purified STC2 protein was applied on the CAM. Taken together, we demonstrate a dual role for STC2 in neuroblastoma. It reduces proliferation of tumor cells in vitro, but increases the invasive potential and induces bleeding, and thereby may facilitate early metastasis. The potential of STC2 as a surrogate marker for metastatic neuroblastoma calls for further investigation. (C) 2009 UICC