Identification of gastric cancer stem cells using the cell surface marker CD44.
Identification of gastric cancer stem cells using the cell surface marker CD44.
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DOI：
10.1002/stem.30
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发表时间：
2009-05
期刊：
影响因子：
5.2
通讯作者：
Wang, Timothy C.
中科院分区：
文献类型：
--
作者：
Takaishi, Shigeo;Okumura, Tomoyuki;Tu, Shuiping;Wang, Sophie S. W.;Shibata, Wataru;Vigneshwaran, Ramanathan;Gordon, Shanisha A. K.;Shimada, Yutaka;Wang, Timothy C.
癌症干细胞（CSC）被定义为肿瘤中独特的亚群，具有启动肿瘤生长和维持肿瘤自我更新的能力。尽管已有证据支持各种实体瘤中存在CSC，但胃CSC的身份尚未见报道。在这项研究中，我们使用细胞表面标记 CD44 从一组人胃癌细胞系中鉴定出了胃癌起始细胞。在6种胃癌细胞系中，MKN-45、MKN-74和NCI-N87这3种细胞系具有相当大的CD44(+)细胞亚群，这些细胞在体外无血清培养基中显示出球状集落形成，并且在体内注射到严重联合免疫缺陷(SCID)小鼠的胃和皮肤时显示出致瘤能力。 CD44(+)胃癌细胞显示出自我更新的干细胞特性和形成分化后代的能力，并产生CD44(-)细胞。通过短发夹RNA敲低CD44可导致SCID小鼠中球状集落形成大大减少，肿瘤产量减少，并且CD44(-)群体在体外和体内的致瘤能力显着降低。其他潜在的 CSC 标志物，如 CD24、CD133、CD166、阶段特异性胚胎抗原 1 (SSEA-1) 和 SSEA-4，或侧群分类，在体外或体内均未显示出与致瘤性的任何相关性。 CD44(+)胃癌细胞对化疗或放疗诱导的细胞死亡的抵抗力增强。这些结果支持了胃CSC的存在，并可能为胃癌的诊断和治疗提供新的方法。
Cancer stem cells (CSCs) have been defined as a unique subpopulation in tumors that possess the ability to initiate tumor growth and sustain tumor self-renewal. Although the evidence has been provided to support the existence of CSCs in various solid tumors, the identity of gastric CSCs has not been reported. In this study, we have identified gastric cancer-initiating cells from a panel of human gastric cancer cell lines using cell surface marker CD44. Among six gastric cancer cell lines, three lines MKN-45, MKN-74, and NCI-N87 had a sizeable subpopulation of CD44(+) cells, and these cells showed spheroid colony formation in serum-free media in vitro as well as tumorigenic ability when injected into stomach and skin of severe combined immunodeficient (SCID) mice in vivo. The CD44(+) gastric cancer cells showed the stem cell properties of self-renewal and the ability to form differentiated progeny and gave rise to CD44(−) cells. CD44 knockdown by short hairpin RNA resulted in much reduced spheroid colony formation and smaller tumor production in SCID mice, and the CD44(−) populations had significantly reduced tumorigenic ability in vitro and in vivo. Other potential CSC markers, such as CD24, CD133, CD166, stage-specific embryonic antigen-1 (SSEA-1), and SSEA-4, or sorting for side population did not show any correlation with tumorigenicity in vitro or in vivo. The CD44(+) gastric cancer cells showed increased resistance for chemotherapy- or radiation-induced cell death. These results support the existence of gastric CSCs and may provide novel approaches to the diagnosis and treatment of gastric cancer.
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影响因子：
29.4
作者：
Dekaney, CM;Rodriguez, JM;Henning, SJ
通讯作者：
Henning, SJ
影响因子：
7.8
作者：
Asakura, Atsushi;Seale, Patrick;Girgis-Gabardo, Adele;Rudnicki, Michael A
通讯作者：
Rudnicki, Michael A
影响因子：
7.3
作者：
Burkert, J.;Otto, W. R.;Wright, N. A.
通讯作者：
Wright, N. A.
影响因子：
12.4
作者：
Eramo, A.;Lotti, F.;De Maria, R.
通讯作者：
De Maria, R.
DOI：
10.1073/pnas.0703478104
发表时间：
2007-06-12
影响因子：
11.1
作者：
Dalerba, Piero;Dylla, Scott J.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.