Downregulation of TGF-beta receptor types II and III in oral squamous cell carcinoma and oral carcinoma-associated fibroblasts.

Downregulation of TGF-beta receptor types II and III in oral squamous cell carcinoma and oral carcinoma-associated fibroblasts.
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口腔鳞状细胞癌和口腔癌相关成纤维细胞中 II 型和 III 型 TGF-β 受体的下调

DOI:
10.1186/1471-2407-11-88
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发表时间:
2011-02-28
期刊:
影响因子:
3.8
通讯作者:
Zhou H
Zhou H
中科院分区:
医学2区
文献类型:
--
作者:
Meng W;Xia Q;Wu L;Chen S;He X;Zhang L;Gao Q;Zhou H

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本研究的目的是检测T-β受体在口腔癌前病变(口腔白斑)、口腔鳞状细胞癌(OSCC)及口腔癌相关成纤维细胞(CAF)中的表达水平,探讨不同类型T-β受体在口腔黏膜癌变过程中的作用。正常口腔组织、口腔扁平苔藓和口腔鳞癌均取自138例未经治疗的患者。通过细胞培养,成功地建立了7个人口腔CAF原代细胞系和6个原代正常成纤维细胞系。用免疫组织化学(IHC)、定量RT-PCR和Western印迹方法检测这三种受体的表达。TβRII和TβRIII在上皮层的IHC信号随着疾病侵袭性的增加而减少(P&lt;0.0 5),TβRI在OLK和OSCC中的表达没有差异(P&gt;0.0 5),而TβRII和TβRIII在基因和蛋白水平上显著低于非小细胞肺癌(P&lt;0.0 5)。外源性表达转化生长因子-β1可显著降低CAF中TβRII和TβRIII的表达(P<0.0 5)。本研究首次证明口腔鳞状细胞癌中TβRII和TβRIII的表达缺失是口腔鳞癌的常见事件。恢复口腔癌组织中TβRII和TβRIII的表达可能为口腔癌的治疗提供新的策略。
The purpose of this study was to assess the expression levels for TβRI, TβRII, and TβRIII in epithelial layers of oral premalignant lesions (oral leukoplakia, OLK) and oral squamous cell carcinoma (OSCC), as well as in oral carcinoma-associated fibroblasts (CAFs), with the final goal of exploring the roles of various types of TβRs in carcinogenesis of oral mucosa. Normal oral tissues, OLK, and OSCC were obtained from 138 previously untreated patients. Seven primary human oral CAF lines and six primary normal fibroblast (NF) lines were established successfully via cell culture. The three receptors were detected using immunohistochemical (IHC), quantitative RT-PCR, and Western blot approaches. IHC signals for TβRII and TβRIII in the epithelial layer decreased in tissue samples with increasing disease aggressiveness (P < 0.05); no expression differences were observed for TβRI, in OLK and OSCC (P > 0.05); and TβRII and TβRIII were significantly downregulated in CAFs compared with NFs, at the mRNA and protein levels (P < 0.05). Exogenous expression of TGF-β1 led to a remarkable decrease in the expression of TβRII and TβRIII in CAFs (P < 0.05). This study provides the first evidence that the loss of TβRII and TβRIII expression in oral epithelium and stroma is a common event in OSCC. The restoration of the expression of TβRII and TβRIII in oral cancerous tissues may represent a novel strategy for the treatment of oral carcinoma.
DOI: 10.1016/j.lungcan.2004.07.977
发表时间: 2004-08-01
期刊: LUNG CANCER
影响因子: 5.3
作者:
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通讯作者: Östman, A
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发表时间: 2008-02-01
期刊: CANCER RESEARCH
影响因子: 11.2
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发表时间: 2002-02-01
影响因子: 2.9
作者:
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DOI: 10.1158/1078-0432.ccr-08-0546
发表时间: 2008-09-15
期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子: --
作者:
Margulis V;Maity T;Zhang XY;Cooper SJ;Copland JA;Wood CG
通讯作者: Wood CG
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DOI: 10.1111/j.1601-0825.2005.01207.x
发表时间: 2006-07-01
期刊: ORAL DISEASES
影响因子: 3.8
作者:
Liu, Y.;Hu, T.;Zhou, H. M.
通讯作者: Zhou, H. M.