Becker Juergen, Volland Sonja, Noskova Ievgeniia, Schramm Alexander, Schweigerer Lothar L, Wilting Joerg
Zentrum Anatomie, Abteilung Anatomie und Zellbiologie, Universitätsmedizin Göttingen, D-37075 Göttingen, Germany.
Int J Oncol. 2008 Jan;32(1):235-40.
Neuroblastoma is the most frequent solid malignancy of children. The most reliable prognostic factor in neuroblastoma is the amplification status of the MYCN oncogene, but exceptions from this rule have been observed. Recently we have demonstrated that keratoepithelin (BIGH3, TGFBI) expression significantly reduces proliferation and invasion of neuroblastomas in vitro and in vivo. In these experiments, we also observed that tissue factor pathway inhibitor 2 (TFPI2, PP5, MSPI), a potent inhibitor of matrix-metalloproteinases, is most prominently up-regulated. As MYCN-amplified neuroblastomas are highly invasive, we sought to determine the interaction between MYCN, keratoepithelin and TFPI2. In this study we provide initial evidence that i) keratoepithelin expression in neuroblastoma inversely correlates with MYCN expression; ii) TFPI2 expression in neuroblastoma also correlates inversely with MYCN expression but positively with keratoepithelin expression and iii) keratoepithelin induces elevated TFPI2 transcript levels in neuroblastoma cells without alterations of MYCN expression.
神经母细胞瘤是儿童最常见的实体恶性肿瘤。神经母细胞瘤最可靠的预后因素是MYCN癌基因的扩增状态，但也观察到了该规则的例外情况。最近我们证明，角蛋白上皮素（BIGH3，TGFBI）的表达在体外和体内均能显著降低神经母细胞瘤的增殖和侵袭。在这些实验中，我们还观察到组织因子途径抑制剂2（TFPI2，PP5，MSPI），一种有效的基质金属蛋白酶抑制剂，上调最为显著。由于MYCN扩增的神经母细胞瘤具有高度侵袭性，我们试图确定MYCN、角蛋白上皮素和TFPI2之间的相互作用。在本研究中，我们提供了初步证据，即：i）神经母细胞瘤中角蛋白上皮素的表达与MYCN的表达呈负相关；ii）神经母细胞瘤中TFPI2的表达也与MYCN的表达呈负相关，但与角蛋白上皮素的表达呈正相关；iii）角蛋白上皮素可诱导神经母细胞瘤细胞中TFPI2转录水平升高，而MYCN的表达无变化。
