Sun Mao, Zhou Wei, Zhang Yun-Yun, Wang Dong-Lin, Wu Xiao-Ling
Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010;
Oncol Lett. 2013 Jun;5(6):1793-1798. doi: 10.3892/ol.2013.1272. Epub 2013 Mar 26.
CD44 has been confirmed as a cancer stem cell marker in a variety of human cancer cell lines and primary tumours, but whether this marker is applicable to gastric cancer (GC) remains unknown. The responses of CD44 GC stem-like cells to chemoradiation and the roles they play in cancer invasion are not well understood. In the present study, cell sorting was applied to the poorly differentiated human GC cells to isolate a pure concentration of the CD44 cell populations (<1% CD44 cells). The stemness properties of the CD44 cell population were confirmed by two 'gold standard' methods; an tumourigenicity assay and an spheroid colony formation assay. In addition, the treatment response was evaluated in CD44 and CD44 cell fractions that underwent chemoradiation. In general, CD44 stem-like cells tended to respond more poorly to chemoradiation than their non-stem-like counterparts. Further experimentation revealed that the CD44 stem-like cells that recorded positive scores in the migration and invasion assay formed invasive tumours . Therefore, we hypothesized that CD44 stem-like cells may significantly express invasion-associated genes. Consistent with this prediction, increased expression of the cancer invasion-related genes matrix metalloproteinase (MMP)-1, MMP-2, epidermal growth factor receptor (EGFR) and cyclooxygenase 2 (COX-2) were detected in the CD44 stem-like cells. To the best of our knowledge, this is the first study that reveals the correlation between CD44 GC cells and cancer invasion. By selectively eliminating CD44 stem-like cells, it may be possible to treat patients with aggressive, non-resectable GCs, as well as preventing the tumours from metastasizing.
CD44已被确认为多种人类癌细胞系和原发性肿瘤中的癌症干细胞标志物，但该标志物是否适用于胃癌（GC）仍不清楚。CD44胃癌干细胞样细胞对放化疗的反应及其在癌症侵袭中所起的作用尚未完全明确。在本研究中，对低分化人胃癌细胞应用细胞分选技术，以分离出纯的CD44细胞群体（CD44细胞<1%）。通过两种“金标准”方法证实了CD44细胞群体的干性特性；一种是致瘤性试验，另一种是球状体集落形成试验。此外，还对接受放化疗的CD44和CD44细胞组分的治疗反应进行了评估。一般来说，CD44干细胞样细胞对放化疗的反应往往比其非干细胞样对应细胞更差。进一步的实验表明，在迁移和侵袭试验中获得阳性评分的CD44干细胞样细胞形成了侵袭性肿瘤。因此，我们假设CD44干细胞样细胞可能显著表达与侵袭相关的基因。与这一预测一致，在CD44干细胞样细胞中检测到癌症侵袭相关基因基质金属蛋白酶（MMP）-1、MMP-2、表皮生长因子受体（EGFR）和环氧合酶2（COX-2）的表达增加。据我们所知，这是第一项揭示CD44胃癌细胞与癌症侵袭之间相关性的研究。通过选择性地消除CD44干细胞样细胞，有可能治疗侵袭性、不可切除的胃癌患者，并防止肿瘤转移。
