Kumamoto H, Kimi K, Ooya K
Division of Oral Pathology, Department of Oral Medicine and Bioregulation, Tohoku University Graduate School of Dentistry, Sendai, Japan.
J Oral Pathol Med. 2001 Nov;30(10):596-602. doi: 10.1034/j.1600-0714.2001.301004.x.
To clarify the possible role of apoptotic cell death in oncogenesis and cytodifferentiation of odontogenic epithelium, apoptosis-related factors--Fas, Fas ligand (FasL), caspase-3 and single-stranded DNA (ssDNA)--were analyzed in ameloblastomas as well as in tooth germs.
Specimens of 5 tooth germs, 29 benign ameloblastomas and 5 malignant ameloblastomas were examined by immunohistochemistry using anti-Fas, FasL, caspase-3 and ssDNA polyclonal antibodies.
Immunoreactivity for Fas and FasL was detected in normal and neoplastic odontogenic epithelial cells. Fas expression in ameloblastomas was slightly lower than that in tooth germs, whereas FasL expression was similar in tooth germs and ameloblastomas. Malignant ameloblastomas showed downregulation of Fas expression and upregulation of FasL expression, as compared with benign ameloblastomas, indicating escape from cell death attack by immune cells. Immunoreactivity for caspase-3 was detected chiefly in cells neighboring the basement membrane in tooth germs and ameloblastomas. Expression of caspase-3 and Fas tended to be low in basal cell ameloblastomas and high in desmoplastic ameloblastomas, as compared with other variants of ameloblastomas. Caspase-3 expression was more intense in malignant ameloblastomas than in tooth germs and benign ameloblastomas. Apoptotic bodies reactive with anti-ssDNA antibody were detected in normal and neoplastic odontogenic epithelial cells detached from the basement membrane. Keratinizing cells in acanthomatous ameloblastomas and granular cells in granular cell ameloblastomas showed increased numbers of apoptotic bodies and increased expression of Fas and caspase-3, as compared with other neoplastic cells. Apoptotic reactions in malignant ameloblastomas were less frequent than in benign ameloblastomas, indicating abnormal regulation of cell turnover in odontogenic epithelial cells.
These apoptosis-related factors were detected in various patterns in normal and neoplastic odontogenic epithelium, suggesting that these factors might be associated with oncogenesis and cytodifferentiation of epithelial odontogenic tumors.
为阐明凋亡性细胞死亡在牙源性上皮肿瘤发生及细胞分化中的可能作用，对成釉细胞瘤及牙胚中的凋亡相关因子——Fas、Fas配体（FasL）、半胱天冬酶-3及单链DNA（ssDNA）进行了分析。
采用抗Fas、FasL、半胱天冬酶-3及ssDNA多克隆抗体，通过免疫组织化学法对5个牙胚、29个良性成釉细胞瘤及5个恶性成釉细胞瘤标本进行检测。
在正常及肿瘤性牙源性上皮细胞中均检测到Fas和FasL的免疫反应性。成釉细胞瘤中Fas的表达略低于牙胚，而FasL的表达在牙胚和成釉细胞瘤中相似。与良性成釉细胞瘤相比，恶性成釉细胞瘤显示Fas表达下调及FasL表达上调，表明其逃避了免疫细胞的细胞死亡攻击。半胱天冬酶-3的免疫反应性主要在牙胚和成釉细胞瘤中紧邻基底膜的细胞中检测到。与其他类型的成釉细胞瘤相比，基底细胞型成釉细胞瘤中半胱天冬酶-3和Fas的表达往往较低，而促结缔组织增生型成釉细胞瘤中则较高。恶性成釉细胞瘤中半胱天冬酶-3的表达比牙胚和良性成釉细胞瘤中更强烈。在从基底膜脱离的正常及肿瘤性牙源性上皮细胞中检测到与抗ssDNA抗体反应的凋亡小体。与其他肿瘤细胞相比，棘皮瘤型成釉细胞瘤中的角化细胞及颗粒细胞型成釉细胞瘤中的颗粒细胞显示凋亡小体数量增加，Fas和半胱天冬酶-3的表达增加。恶性成釉细胞瘤中的凋亡反应比良性成釉细胞瘤中少，表明牙源性上皮细胞的细胞更新存在异常调节。
在正常及肿瘤性牙源性上皮中以多种模式检测到这些凋亡相关因子，提示这些因子可能与牙源性上皮肿瘤的发生及细胞分化有关。
