Zhang Shengliang, Shang Yanna, Chen Tie, Zhou Xin, Meng Wengtong, Fan Chuanwen, Lu Ran, Huang Qiaorong, Li Xue, Hong Xu, Zhou Zongguang, Hu Jiankun, Mo Xianming
Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
Health Science Center, Institute of Molecular Medicine, Shenzhen University, Shenzhen, 518060, China.
J Cancer Res Clin Oncol. 2017 Sep;143(9):1687-1699. doi: 10.1007/s00432-017-2417-3. Epub 2017 Apr 20.
Metastasis is a leading cause of cancer-related-deaths worldwide. Recently, cancer stem cells (CSCs) have been believed to be responsible for tumor initiation and metastasis, but till now, difference of cellular features and behaviors between CSCs from tumor tissues (TCSCs) and circulation (CCSCs) remains largely unknown, which hinders the progression of targeted therapies for metastasis.
Here, we provide the features of circulating gastric cancer stem cells (CGCSCs) isolated from human gastric adenocarcinoma. The CGCSCs and TGCSCs were culture in a same serum free stem cell culture medium, however the morphology are different with each other. EMT-associated markers were measured by Immunofluorescence, Western Blotting, and RT-PCR methods, and the results indicated that the CGCSCs and TGCSCs carry different epithelial-mesenchymal features. And then, proliferation and apoptosis assays revealed that the CGCSCs exhibited characteristics of higher proliferation and resistance to apoptosis in vitro. Soft agar assay and nude mice tumorigenicity assay displayed strong tumorigenicity of CGCSCs. Finally, Matrigel invasion assays and in vivo experimental metastasis assay were also performed, which demonstrated that CGCSCs carry high invasive and metastatic capabilities than TGCSCs.
As expected, the CGCSCs indeed showed extremely invasive and metastatic properties. They also exhibited distinctive mesenchymal phenotypes, high self-renewal, proliferative capabilities, tumor induction and low apoptosis. Interestingly, CGCSCs show small cell-size than TGCSCs (tissue gastric cancer stem cells). The findings might help us to understand the biological characteristic of CGCSCs deeply, and give light to strategies for cancer therapies.
转移是全球癌症相关死亡的主要原因。最近，癌症干细胞（CSCs）被认为是肿瘤起始和转移的原因，但到目前为止，肿瘤组织中的癌症干细胞（TCSCs）和循环中的癌症干细胞（CCSCs）之间的细胞特征和行为差异仍 largely 未知，这阻碍了转移靶向治疗的进展。
在此，我们提供了从人胃腺癌中分离出的循环胃癌干细胞（CGCSCs）的特征。CGCSCs 和 TGCSCs 在相同的无血清干细胞培养基中培养，然而它们的形态彼此不同。通过免疫荧光、蛋白质印迹和 RT-PCR 方法测量 EMT 相关标志物，结果表明 CGCSCs 和 TGCSCs 具有不同的上皮 - 间充质特征。然后，增殖和凋亡分析表明 CGCSCs 在体外表现出更高的增殖和抗凋亡特征。软琼脂分析和裸鼠致瘤性分析显示 CGCSCs 具有很强的致瘤性。最后，还进行了基质胶侵袭分析和体内实验性转移分析，结果表明 CGCSCs 比 TGCSCs 具有更高的侵袭和转移能力。
正如预期的那样，CGCSCs 确实表现出极强的侵袭和转移特性。它们还表现出独特的间充质表型、高自我更新、增殖能力、肿瘤诱导能力和低凋亡率。有趣的是，CGCSCs 的细胞大小比 TGCSCs（组织胃癌干细胞）小。这些发现可能有助于我们深入了解 CGCSCs 的生物学特性，并为癌症治疗策略提供启示。
