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Significance of dipeptidyl peptidases as marker enzyme of oral cancer

二肽基肽酶作为口腔癌标志酶的意义

基本信息

批准号：
03670944
负责人：
URADE Masahiro
金额：
$ 1.34万
依托单位：
Hyogo College of Medicine (1992)Osaka University (1991)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670944/
关键词：
Serum dipeptidyl peptidase IV Serum dipeptidyl peptidase II Tumor-burden marker Hamster buccal pouch A model of oral cancer ハムスター頬襄シリアンハムスタ-ジメチルベンツアントラセン頬嚢発癌血清ジペプチジルペプチダ-ゼ活性担癌マ-カ-

项目摘要

Dipeptidyl peptidases(DPP) are classified into four types, I-IV, according to the substrate specificity. Among them, DPP IV specifically hydrolyzes N-terminal glycylprolyl and is present in microsomal membranes, and DPP II specifically cleaves N-terminal lysylalanyl and is mainly in lysosomes. We have reported that serum DPP IV activity was significantly decreased in oral cancer patients whereas serum DPP II activity was significantly increased, suggesting that they become a possible marker of oral cancer. However, what is the precise mechanism for changing serum enzyme activities and at which stage of carcinogenesis the serum enzyme level begins to be changed, are still unknown.In the present study, the enzyme expression in the precancerous and cancerous tissues and the change of serum enzyme activity level were investigated using hamster buccal pouch carcinogenesis with 9,10-dimethyl-1,2-benzanthracene (DMBA). The serum DPP IV level was decreased gradually from the 8th to 10th week when papillomas were induced by DMBA application. The enzyme level was further decreased as carcinoma in situ or early invasive carcinoma developed (p<0.001), and reached to less than half of the normal level at the time when tumors were diagnosed as squamous cell carcinoma histologically. This enzyme level was increased by tumor excision and decreased again by tumor recurrence toward death. In contrast, serum DPP II activity showed a minor increase in the early stage of carcinogenesis, and increased significantly as squamous cell carcinoma developed (p<0.01). This enzyme activity tended to change reciprocally to DPP IV activity. Immunohistological staining with rabbit anti-rat DPP IV serum did not detect the significant difference between normal and precancerous or cancerous tissues.These findings suggest that serum DPP IV and II activities might be useful as tumor-burden markers ; especially, DPP IV activity, which changed from the early stage of carcinogenesis.

根据底物的特异性，二肽基肽酶(DPP)可分为I-IV四种类型。其中，DPP IV特异性地降解N-末端甘氨酰丙基，存在于微粒体膜中；DPP II特异性地裂解N-末端赖氨酰基，主要存在于溶酶体内。我们已报道口腔癌患者血清DPP IV活性显著降低，而DPP II活性显著升高，提示它们可能成为口腔癌的标志物。然而，血清酶活性变化的确切机制是什么，以及血清酶水平在癌变的哪个阶段开始变化，目前尚不清楚。本研究采用9，10-二甲基-1，2-苯并菲(DMBA)诱发仓鼠颊囊癌，研究了癌前病变和癌组织中酶的表达及血清酶活性水平的变化。DMBA诱发乳头状瘤后第8~10周，血清DPP IV水平逐渐下降。随着原位癌或早期浸润性癌的发展，酶水平进一步降低(p&lt；0.001)，达到组织学诊断为鳞状细胞癌时正常水平的不到一半。这种酶水平在肿瘤切除后升高，在肿瘤复发接近死亡时再次降低。相反，血清DPP II活性在癌变早期略有升高，并随着鳞癌的发展而显著升高(p&lt；0.01)。该酶活性与DPP IV活性呈反向变化趋势。兔抗大鼠DPP IV血清免疫组织化学染色未检测到正常组织与癌前病变或癌组织之间的显著差异，提示血清DPP IV和DPP II活性可作为肿瘤负荷标记物，尤其是DPP IV活性在癌变早期发生变化。