Possible Involvement of Pancreatic Fatty Infiltration in Pancreatic Carcinogenesis
Possible Involvement of Pancreatic Fatty Infiltration in Pancreatic Carcinogenesis
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发表时间：
2016
影响因子：
0.2
通讯作者：
M. Hori;M. Mutoh;T. Imai;H. Nakagama;Mami Takahashi
中科院分区：
文献类型：
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作者：
M. Hori;M. Mutoh;T. Imai;H. Nakagama;Mami Takahashi
胰腺癌在早期阶段很难诊断，是最致命的人类癌症之一。因此，明确其主要危险因素、预测因素及病因学意义重大。在这里，我们关注胰腺的脂肪浸润，并认为它可能是胰腺癌的一个危险因素。胰腺的脂肪浸润被观察为异位脂肪细胞浸润胰腺组织，并且与肥胖和糖尿病的患病率正相关，肥胖和糖尿病是胰腺癌的危险因素。然而，脂肪浸润是否是胰腺癌的主要危险因素尚未确定。近年来的临床研究表明，胰腺脂肪浸润与胰腺癌前病变或导管腺癌呈正相关。动物实验研究也显示胰腺脂肪浸润与胰腺癌前病变或导管腺癌发展之间的关联。叙利亚金仓鼠，这是敏感的化学致癌物质在胰腺，发展脂肪浸润胰腺随着年龄的增长。高脂饮食和化学致癌物的结合诱导K-ras突变增加了胰腺脂肪浸润的严重性。因此，胰腺的脂肪浸润建议通过K-ras激活突变促进胰腺癌的发生。据推测，胰腺脂肪浸润引起的脂肪因子和炎症及增殖相关因子的表达增加可能有助于胰腺癌前病变或导管腺癌的发展。越来越多的证据表明，除了抑制Ras活化之外，调节胰腺中脂肪浸润的方法可以被认为是预防胰腺癌的策略。
Pancreatic cancer is difficult to diagnose in its early stage and is one of the most lethal human cancers. Thus, it is important to clarify its major risk factors, predictive factors and etiology. Here, we focus on fatty infiltration of the pancreas and suggest that it could be a risk factor for pancreatic cancer. Fatty infiltration of the pancreas is observed as ectopic adipocytes infiltrating the pancreatic tissue and is positively correlated with obesity and the prevalence of diabetes mellitus, which are risk factors for pancreatic cancer. However, whether fatty infiltration is a major risk factor for pancreatic cancer has not been established. Recent clinical studies show there is a positive correlation between fatty infiltration of the pancreas and pancreatic precancerous lesions or ductal adenocarcinomas. Animal experimental studies also show an association between fatty infiltration of the pancreas and pancreatic precancerous lesions or ductal adenocarcinomas development. Syrian golden hamsters, which are sensitive to chemical carcinogens in the pancreas, develop fatty infiltration of the pancreas with age. The combination of a high-fat diet and a chemical carcinogen that induces a K-ras mutation increases the severity of fatty infiltration of the pancreas. Thus, fatty infiltration of the pancreas is suggested to promote pancreatic carcinogenesis via a K-ras activating mutation. It is assumed that increased expression of adipokines and of inflammatory and proliferation-associated factors elicited by fatty infiltration of the pancreas may contribute to pancreatic precancerous lesions or ductal adenocarcinomas development. Accumulating evidence suggests that in addition to suppression of Ras activation, methods to modulate fatty infiltration in the pancreas can be considered as a strategy for preventing pancreatic cancer.