Role of squamous cell carcinoma antigen 1 expression in the invasive potential of head and neck squamous cell carcinoma
Role of squamous cell carcinoma antigen 1 expression in the invasive potential of head and neck squamous cell carcinoma
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DOI：
10.1002/hed.20293
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发表时间：
2006-01-01
影响因子：
2.9
通讯作者：
Komune, S
中科院分区：
文献类型：
--
作者：
Nakashima, T;Yasumatsu, R;Komune, S
背景丝氨酸蛋白酶在肿瘤的侵袭和转移中起重要作用，其抑制剂丝氨酸蛋白酶抑制剂（Serine protease inhibitors，serpins）是肿瘤治疗的重要靶点。在染色体18 q21上，有一簇丝氨酸蛋白酶抑制剂：maspin，headpin和鳞状细胞癌抗原1（SCCA 1）/SCCA 2。其他人和我们已经报道，这些丝氨酸蛋白酶抑制剂的表达下调，在头颈部鳞状细胞癌（HNSCC）细胞与正常鳞状上皮细胞相比。在这项研究中，我们假设，表达SCCA 1是生物学上不利的HNSCC cells.Methods，HNSCC细胞系转染与哺乳动物表达载体与SCCA 1 cDNA。在体外增殖，迁移，或侵袭潜力（基质胶测定）的转染进行了测定。采用裸鼠口腔底模型观察其体内生长和侵袭情况。SCCA 1的表达没有改变已建立的HNSCC细胞的体外生长速率。然而，SCCA 1的表达显着抑制体外侵袭基质胶测定。此外，SCCA 1的表达还可抑制裸鼠体内的生长和侵袭。在HNSCC细胞系中过表达SCCA 1抑制其侵袭潜力。丝氨酸蛋白酶抑制剂SCCA 1表达的缺失可能在HNSCC的恶性进展中发挥作用。(c)2005 Wiley Periodicals，Inc.
Background. Serine proteases have important roles in tumor invasion and metastasis, and their inhibitors, serine protease inhibitors (serpins), are attractive targets for therapeutic strategies. On chromosome 18q21, there is a cluster of serpins: maspin, headpin, and squamous cell carcinoma antigen 1 (SCCA1)/SCCA2. Others and we have reported that the expression of these serpins is downregulated in head and neck squamous cell carcinoma (HNSCC) cells compared with normal squamous epithelial cells. In this study, we hypothesized that expression of SCCA1 is biologically disadvantageous to HNSCC cells.Methods, HNSCC cell lines were transfected with a mammalian expression vector with SCCA1 cDNA. In vitro proliferation, migration, or invasive potential (matrigel assay) of the transfectants were assayed. In addition, the in vivo growth and invasion was analyzed using the floor-of-mouth model of nude mice.Results. SCCA1 expression did not alter the in vitro growth rate of established HNSCC cells. However, SCCA1 expression significantly inhibited the in vitro invasion in matrigel assays. Furthermore, the in vivo growth and invasion in nude mice was also inhibited by SCCA1 expression.Conclusions. Overexpression of SCCA1 in a HNSCC cell line inhibited its invasive potential. Loss of expression of the serpin SCCA1 may play a role in the malignant progression of HNSCC. (c) 2005 Wiley Periodicals, Inc.