The Biological Role of Headpin in Head and Neck Cancer

Headpin 在头颈癌中的生物学作用

• 批准号: 13671786
• 负责人: NAKASHIMA Torahiko
• 金额: $ 2.24万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671786/
• 关键词: serpin; headpin; maspin; SCC Antigen; Head and Neck Cancer; 遺伝子治療

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, which is recognized as a region for frequent loss of heterozygosity (LOH) in head and neck squamous cell carcinoma (HNSCC), there is a cluster of serping; maspin, headpin, and SCCA1. Others and we have reported that the expression of maspin, headpin and SCCA1 are down-regulated in HNSCC cells as compared to normal squamous epithelial cells. In this study, we hypothesized that expression of these serpins are biologically disadvantageous to HNSCC cells. We also hypothesized that alterations in these serpin expression will produce differences in the phenotypic behavior of oral SCC tumors in patients. Established HNSCC cell lines were stably transfected with a mammalian expression vector with SCCA1 or headpin cDNA. In vitro proliferation, migration, or invasive potential (Matrigel assay) of … More the transfectans were assayed. In addition, archival paraffin embedded specimens of primary tongue tumors from patients were analyzed for SCCA1, maspin, and headpin mRNA and/or protein expression using quantitative RT-PCR and/or imunohistochemistry respectively. The relationship between the expression and invasiveness, clinical courses of the patients were analyzed. Headpin or SCCA1 expression did not alter the in vitro growth rate of established HNSCC cells. However, SCCA1 and headpin expression both significantly inhibited the in vitro invasion in matrigel assays. The absence of maspin expression in oral SCC specimens was found more frequently in cases of subsequent cervical lymph node metastasis than in cases without metastasis.SCCA1 and headpin may function to inhibit the invasive potential of HNSCC. Loss of expression of 18q21 serpins; maspin, headpin and SCCA1 may play a role in the malignant progression of HNSCC.Serpins which locate as 18q21; maspin, headpin and SCCA1 have potential to be the molecular targets in the treatment of HNSCC. Less

丝氨酸蛋白酶在肿瘤的侵袭和转移中起着重要作用，其抑制物、丝氨酸蛋白酶抑制物(Serpins)是治疗策略的重要靶点。在被认为是头颈部鳞状细胞癌(HNSCC)频繁杂合性缺失(LOH)的18q21号染色体上，有一簇锯齿状片段：maspin、Headpin和SCCA1。与正常鳞状上皮细胞相比，HNSCC细胞中maspin、Headpin和SCCA1的表达下调。在这项研究中，我们假设这些蛇的表达对HNSCC细胞在生物学上是不利的。我们还假设，这些丝氨酸蛋白表达的改变将导致患者口腔鳞状细胞癌肿瘤表型行为的差异。将含有SCCA1或Headpin基因的真核表达载体稳定地导入HNSCC细胞系。…的体外增殖、迁移或侵袭潜能(Matrigel实验)更多地检测转染素。另外，采用定量RT-PCR和/或免疫组织化学方法分别检测了SCCA1、maspin和Headpin基因在舌癌中的表达。分析其表达与肿瘤侵袭性、临床病程的关系。Headpin或SCCA1的表达不改变已建立的HNSCC细胞的体外生长速度。然而，在Matrigel实验中，SCCA1和Headpin的表达都显著地抑制了体外侵袭。口腔鳞状细胞癌组织中maspin表达缺失在有颈淋巴转移的病例中较无转移病例多见，SCCA1和Headpin可能发挥抑制HNSCC侵袭潜能的作用。18q21 Serpins表达缺失；maspin、Headpin和SCCA1可能在HNSCC的恶性进展中起作用；位于18q21的Serpins有可能成为治疗HNSCC的分子靶点。较少

项目成果

Masuda M, Suzui M, Yasumatsu R, Nakashima T, Kuratomi Y, Azuma K, Tomita K, Komiyama S, Weinstein IB.: "Constitutive activation of signal transducers and activators of transcription 3 correlates with cyclin D1 overexpression and may provide a novel propgn

Masuda M、Suzui M、Yasumatsu R、Nakashima T、Kuratomi Y、Azuma K、Tomita K、Komiyama S、Weinstein IB.：“信号转导子和转录激活子 3 的组成性激活与细胞周期蛋白 D1 过度表达相关，并可能提供一种新的预防方法

Yasumatsu R, Nakashima T, Azuma K, Hirakawa N, Kuratomi Y, Tomita K, Cataltepe S, Silverman GA, Clayman GL, Komiyama S.: "SCCA1 expression in T-lymphocytes peripheral to cancer cells is associated with the elevation of serum SCC antigen in squamous cell c

Yasumatsu R、Nakashima T、Azuma K、Hirakawa N、Kuratomi Y、Tomita K、Cataltepe S、Silverman GA、Clayman GL、Komiyama S.：“癌细胞外周 T 淋巴细胞中 SCCA1 的表达与血清 SCC 升高相关

Yasumatsu R, Nakashima T, Kuratomi Y, Komiyama S.: "Postpartum hypercalcemia in a patient with previous thyroid carcinoma: a report of 2 cases."Nippon Jibiinkoka Gakkai Kaiho.. Aug;105(8). 897-900 (2002)

Yasumatsu R、Nakashima T、Kuratomi Y、Komiyama S.：“既往甲状腺癌患者的产后高钙血症：2 例报告。”Nippon Jibiinkoka Gakkai Kaiho.. Aug；105(8)。

Yasumatsu R, Nakashima T, Hirakawa N, Kumamoto Y, Kuratomi Y, Tomita K, Komiyama S.: "Maspin expression in stage I and II oral tongue squamous cell carcinoma"Head Neck. 23(11). 962-966 (2001)

Yasumatsu R、Nakashima T、Hirakawa N、Kumamoto Y、Kuratomi Y、Tomita K、Komiyama S.：“I 期和 II 期口腔舌鳞状细胞癌中的 Maspin 表达”头颈。

Masuda M, Suzui M, Yasumatu R, Nakashima T et al.: "Constitutive activation of signal transducers and activators of transcription 3 correlates with cyclin D1 overexpression and may provide a novel prognostic marker in head and neck squamous cell carcinoma

Masuda M、Suzui M、Yasumatu R、Nakashima T 等人：“信号转导子和转录激活子 3 的组成性激活与细胞周期蛋白 D1 过度表达相关，可能为头颈鳞状细胞癌提供一种新的预后标志物