Initiation and Maintenance of Gastric Cancer: A Focus on CD44 Variant Isoforms and Cancer Stem Cells.
Initiation and Maintenance of Gastric Cancer: A Focus on CD44 Variant Isoforms and Cancer Stem Cells.
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DOI：
10.1016/j.jcmgh.2017.03.003
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发表时间：
2017-07
影响因子：
7.2
通讯作者：
Zavros Y
中科院分区：
文献类型：
--
作者：
Zavros Y
胃癌是癌症相关死亡的第三大常见原因。虽然美国胃癌的发病率相对较低，但在一些国家，包括日本和韩国，胃癌的发病率仍然明显较高。癌症干细胞和肿瘤微环境之间的相互作用可以对肿瘤特征产生实质性影响，并导致异质性。负责维持恶性肿瘤干细胞在人类胃癌的肿瘤微环境中的机制在很大程度上是未知的。肿瘤细胞和遗传异质性有助于从头内在或治疗诱导的耐药克隆的出现和最终的肿瘤复发。尽管化疗通常能够诱导肿瘤细胞死亡，但许多癌症患者由于未能有效靶向癌症干细胞而经历复发，癌症干细胞被认为是关键的肿瘤起始细胞。在胃内的干细胞群体中，在慢性幽门螺杆菌感染期间可能被靶向并改变成肿瘤起始细胞的是由分化簇（CD）44细胞表面受体标记的那些细胞。CD44可变同种型（CD44v）已经被认为是恶性转化中的关键参与者，因此它们的表达是高度限制和特异性的，不像典型的CD44标准同种型。总体而言，CD44v，特别是CD44v9，被认为是胃癌细胞的标志，有助于增加化疗或放射诱导的细胞死亡的抗性。本文就细菌感染对胃干细胞的影响以及CD44 v在胃癌发生、发展中的作用作一综述。
Gastric cancer is the third most common cause of cancer-related death. Although the incidence of gastric cancer in the United States is relatively low, it remains significantly higher in some countries, including Japan and Korea. Interactions between cancer stem cells and the tumor microenvironment can have a substantial impact on tumor characteristics and contribute to heterogeneity. The mechanisms responsible for maintaining malignant cancer stem cells within the tumor microenvironment in human gastric cancer are largely unknown. Tumor cell and genetic heterogeneity contribute to either de novo intrinsic or the therapy-induced emergence of drug-resistant clones and eventual tumor recurrence. Although chemotherapy often is capable of inducing cell death in tumors, many cancer patients experience recurrence because of failure to effectively target the cancer stem cells, which are believed to be key tumor-initiating cells. Among the population of stem cells within the stomach that may be targeted during chronic Helicobacter pylori infection and altered into tumor-initiating cells are those cells marked by the cluster-of-differentiation (CD)44 cell surface receptor. CD44 variable isoforms (CD44v) have been implicated as key players in malignant transformation whereby their expression is highly restricted and specific, unlike the canonical CD44 standard isoform. Overall, CD44v, in particular CD44v9, are believed to mark the gastric cancer cells that contribute to increased resistance for chemotherapy- or radiation-induced cell death. This review focuses on the following: the alteration of the gastric stem cell during bacterial infection, and the role of CD44v in the initiation, maintenance, and growth of tumors associated with gastric cancer.