Insulin-like growth factor 2 mRNA-binding protein-3 as a marker for distinguishing between cutaneous squamous cell carcinoma and keratoacanthoma.
Insulin-like growth factor 2 mRNA-binding protein-3 as a marker for distinguishing between cutaneous squamous cell carcinoma and keratoacanthoma.
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DOI：
10.3892/ijo.2016.3323
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发表时间：
2016-03
影响因子：
5.2
通讯作者：
Naito Z
中科院分区：
文献类型：
--
作者：
Kanzaki A;Kudo M;Ansai S;Peng WX;Ishino K;Yamamoto T;Wada R;Fujii T;Teduka K;Kawahara K;Kawamoto Y;Kitamura T;Kawana S;Saeki H;Naito Z
在皮肤肿瘤的组织病理学诊断中，火山口状结构的鳞状细胞癌（SCC）和角化棘皮瘤（KA）的鉴别诊断往往比较困难，因此准确了解SCC和KA的生物学特征并确定可靠的标志物是关键问题。胰岛素样生长因子2 mRNA结合蛋白3（IGF 2BP 3，也称为IMP3）被认为是一种真正的癌胚蛋白，在多种肿瘤中过表达并参与细胞增殖、迁移和侵袭。然而，IMP3在皮肤SCC和KA中的作用尚未得到充分研究。因此，我们重点研究了IMP3在SCC和KA中的生物学功能。在人皮肤SCC细胞系HSC-1和HSC-5以及人角质形成细胞系中，HaCaT、IMP3 mRNA水平显著高于正常人皮肤。IMP3表达的敲低降低了HSC-1的增殖，并显著降低了HSC-1和HSC-5的侵袭。相反，IMP3的敲低并不显著影响HaCaT细胞的侵袭。在SCC和KA组织的免疫组化研究中，SCC中基底上细胞层的Ki-67标记指数（LI）显著高于KA组织和SCC和KA相邻的无肿瘤边缘（TFM）。大多数SCC组织表达IMP3强阳性，但KA组织和TFM大多为IMP3阴性。IMP3阳性组基底上细胞层Ki-67 LI明显高于IMP3阴性组。这些结果表明，IMP3起着重要的作用，在增殖，更重要的是，在SCC的侵袭，并可能是一个合适的标志物SCC的火山口状架构和KA的组织病理学诊断。此外，IMP3可能是SCC的新治疗靶点。
In the histopathological diagnosis of cutaneous tumors, the differential diagnosis of squamous cell carcinoma (SCC) with crateriform architecture and keratoacanthoma (KA) is often difficult so an accurate understanding of the biological features and the identification of reliable markers of SCC and KA are crucial issues. Insulin-like growth factor 2 mRNA-binding protein-3 (IGF2BP3, also known as IMP3) is thought of as a bona fide oncofetal protein, which is overexpressed and is involved in cell proliferation, migration, and invasion in several kinds of tumors. However, the role of IMP3 in cutaneous SCC and KA has not been well studied. Therefore, we focused on studying the biological functions of IMP3 in SCC and KA. In human skin SCC cell lines, HSC-1 and HSC-5, and the human keratinocyte cell line, HaCaT, IMP3 mRNA levels were significantly higher than that of normal human skin. The knockdown of IMP3 expression reduced the proliferation of HSC-1, and significantly reduced invasion by HSC-1 and HSC-5. In contrast, the knockdown of IMP3 did not significantly affect invasion by HaCaT cells. In immunohistochemical studies of SCC and KA tissues, the Ki-67 labeling index (LI) of the suprabasal cell layer was significantly higher in SCC, compared with KA tissues and the tumor-free margin (TFM) adjacent to SCC and KA. Most SCC tissues stained strongly positive for IMP3, but KA tissues and TFM were mostly negative for IMP3. The Ki-67 LI of the IMP3-positive group was significantly higher than that of the IMP3-negative group in the suprabasal cell layer of SCC. These results suggest that IMP3 plays an important role in proliferation and, more significantly, in the invasion of SCC, and may be a suitable marker for the histopathological diagnosis of SCC with a crateriform architecture and KA. Furthermore, IMP3 may potentially be a new therapeutic target for SCC.