Bile ductular cell reaction with senescent hepatocytes in chronic viral hepatitis is lost during hepatocarcinogenesis
Bile ductular cell reaction with senescent hepatocytes in chronic viral hepatitis is lost during hepatocarcinogenesis
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DOI：
10.1111/j.1440-1827.2009.02395.x
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发表时间：
2009-07-01
影响因子：
2.2
通讯作者：
Nakanuma, Yasuni
中科院分区：
文献类型：
--
作者：
Ikeda, Hiroko;Sasaki, Motoko;Nakanuma, Yasuni
细胞衰老被定义为不可逆的细胞停滞，并且可以作为防止肿瘤发生的保护措施。这一机制在慢性病毒性肝炎相关的肝癌发生中进行了研究。通过使用手术切除或楔形活检肝标本87例慢性病毒性肝炎患者，其中35个肿瘤结节（异型增生结节和肝细胞癌）并发症，P21的表达和衰老相关的β半乳糖苷酶活性，衰老的标志物，进行了检查。所有这些肿瘤性结节在肿瘤内都有汇管区。肝硬化患者肝细胞表达衰老标志物和细胞角蛋白（CK）7阳性的胆管，包括肝祖细胞样细胞在间隔周围区域增加。有趣的是，这些细胞似乎形成了一个解剖复合体，在肿瘤结节内的门静脉周围区域完全消失。在三分之一的肿瘤结节中，CK7阳性的小肿瘤肝细胞类似于肝祖细胞，在汇管区周围呈带状增殖。总之，门静脉周围或间隔周围区域的衰老肝细胞和包括肝祖细胞样细胞在内的小管细胞复合体的丧失可能与肝硬化中肿瘤性肝细胞的出现及其增殖以及随后的肿瘤性结节有关。CK7阳性的小肿瘤肝细胞类似肝祖细胞的带状增殖可能在早期肝癌发生过程中发展。
Cellular senescence is defined as irreversible cell arrest and could work as a safeguard against tumorigenesis. This mechanism was examined in chronic viral hepatitis-related hepatocarcinogenesis. By using surgical resected or wedge biopsied liver specimens from 87 chronic viral hepatitis patients in whom 35 neoplastic nodules (dysplastic nodules and hepatocellular carcinoma) were complicated, P21 expression and senescence-associated beta galactosidase activity, a marker of senescence, were examined. All of these neoplastic nodules harbored portal tracts within the tumors. Hepatocytes expressing senescence markers and cytokeratin (CK)7-positive bile ductules including hepatic progenitor-like cells were increased in periseptal areas in cirrhosis. Interestingly, these cells appeared to form an anatomical complex that was completely lost in the periportal areas within the neoplastic nodules. In one-third of the neoplastic nodules, CK7-positive small neoplastic hepatocytes resembling hepatic progenitor cells proliferated zonally around the portal tracts. In conclusion, loss of a complex of senescent hepatocytes and ductular cell including hepatic progenitor-like cells in the periportal or periseptal areas may be associated with emergence of neoplastic hepatocytes and their proliferation followed by neoplastic nodules arising in liver cirrhosis. Zonal proliferation of CK7-positive small neoplastic hepatocytes resembling hepatic progenitor cells may develop during early hepatocarcinogenesis.