Afrasiabi Kambiz, Zhou Yi-Hong, Fleischman Angela
Department of Medicine, University of California, Irvine, CA, USA.
Department of Surgery, University of California, Irvine, CA, USA.
Genes Cancer. 2015 May;6(5-6):214-9. doi: 10.18632/genesandcancer.64.
Chronic inflammation in well-defined mouse models such as Giα2 knock out mouse has been shown to trigger formation and expansion of hypoxic niches and also leads to up regulation of NFĸB, offering cells which have adapted their genetic machinery to hypoxia a unique survival advantage. These adapted cells have been shown to acquire stem cell-like capabilities as shown by up regulation of stem cell markers. Such long lived cells become permanent residents in sub mucosa and acquire a malignant phenotype from long-term exposure to noxious environmental agents due to a barrier defect secondary to down regulation of barrier proteins such as Zo1 and Occludin. Indeed mitotic spindle disorientation in such mice has been proposed as another contributory factor to malignant transformation. Sterilization of bowel lumen of these mice through different techniques has prevented malignant transformation in the presence of chronic inflammation. These facts stand strongly against chronic inflammation as a true driver of carcinogenesis but clearly support its role in facilitating the emergence of the neoplastic clone.
在明确的小鼠模型（如Giα2基因敲除小鼠）中，慢性炎症已被证明会触发缺氧微环境的形成和扩张，还会导致NFĸB上调，为那些已使其遗传机制适应缺氧的细胞提供独特的生存优势。这些适应后的细胞已被证明获得了干细胞样能力，如干细胞标志物上调所示。这种长寿细胞成为黏膜下层的永久居民，并由于屏障蛋白（如Zo1和闭合蛋白）下调导致的屏障缺陷，长期暴露于有害环境因素而获得恶性表型。事实上，已有人提出此类小鼠中的有丝分裂纺锤体方向异常是恶性转化的另一个促成因素。通过不同技术对这些小鼠的肠腔进行除菌，在存在慢性炎症的情况下可预防恶性转化。这些事实有力地反驳了慢性炎症是致癌的真正驱动因素这一观点，但明确支持其在促进肿瘤克隆出现方面的作用。
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