Autophagy is activated in pancreatic cancer cells and correlates with poor patient outcome
Autophagy is activated in pancreatic cancer cells and correlates with poor patient outcome
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DOI：
10.1111/j.1349-7006.2008.00893.x
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发表时间：
2008-09-01
期刊：
影响因子：
5.7
通讯作者：
Ochiai, Atsushi
中科院分区：
文献类型：
--
作者：
Fujii, Satoshi;Mitsunaga, Shuichi;Ochiai, Atsushi
由于自主增殖的癌细胞经常暴露于缺氧条件下，因此必须有一种替代代谢途径，如自噬，使它们能够在氧气和葡萄糖耗尽时获得能量。我们先前报道发现，自噬实际上有助于体外和体内结直肠癌中癌细胞的存活。胰腺癌仍然是一种毁灭性的和知之甚少的恶性肿瘤，并且已知胰腺癌中的缺氧会增加其恶性潜能。在本研究中，档案胰腺癌组织从71例治疗性胰腺切除术。通过用抗LC3抗体进行免疫组织化学染色来评估自噬，因为LC3是自噬的关键组分并且已被用作自噬的标志物。结果显示，胰腺癌组织周边区域LC3强表达与预后差（P = 0.0170）和无病期短（P = 0.0118）相关。两个最显着的相关性之间的临床病理因素的测试被发现之间的外周强度水平的LC 3表达和肿瘤大小（P = 0.0098）或肿瘤坏死（P = 0.0127）。活化的自噬与胰腺癌细胞有关，自噬被认为是对癌症微环境中因素的反应，如缺氧和营养供应不足。这是第一个报道胰腺癌中自噬的临床病理学意义的研究。
Because autonomous proliferating cancer cells are often exposed to hypoxic conditions, there must be an alternative metabolic pathway, such as autophagy, that allows them to obtain energy when both oxygen and glucose are depleted. We previously reported finding that autophagy actually contributes to cancer cell survival in colorectal cancers both in vitro and in vivo. Pancreatic cancer remains a devastating and poorly understood malignancy, and hypoxia in pancreatic cancers is known to increase their malignant potential. In the present study archival pancreatic cancer tissue was retrieved from 71 cases treated by curative pancreaticoduodenectomy. Autophagy was evaluated by immunohistochemical staining with anti-LC3 antibody, as LC3 is a key component of autophagy and has been used as a marker of autophagy. The results showed that strong LC3 expression in the peripheral area of pancreatic cancer tissue was correlated with a poor outcome (P = 0.0170) and short disease-free period (P = 0.0118). Two of the most significant correlations among the clinicopathological factors tested were found between the peripheral intensity level of LC3 expression and tumor size (P = 0.0098) or tumor necrosis (P = 0.0127). Activated autophagy is associated with pancreatic cancer cells, and autophagy is thought to be a response to factors in the cancer microenvironment, such as hypoxia and poor nutrient supply. This is the first study to report the clinicopathological significance of autophagy in pancreatic cancer.