Cancer Institute of the People's Liberation Army, Xinqiao Hospital, Third Military Medical University, 29 Xinqiao Main Street, Chongqing 400037, People's Republic of China.
Mol Cell Biochem. 2011 Sep;355(1-2):241-8. doi: 10.1007/s11010-011-0860-z. Epub 2011 May 7.
There is increasing evidence that cancer stem cells contribute to the initiation and propagation of many tumor. Therefore, to find out and identify the metastatic tumor stem-like cells in Lewis lung cancer cell line (LLC), the expression of CXCR4 was measured in LLC by flow cytometry and observed by laser scanning confocal microscope (LSCM). After the CXCR4(+) LLC cell was isolated from LLC by magnetic cell sorting, its properties were evaluated by their tumorigenic and metastatic potentials. CXCR4(+) cells were counted for 0.18% of the total number of LLC, and immunofluorescent staining cells were identified by LSCM. CXCR4(+) LLC suspension cultured in a serum-free medium, cell spheres expressed a high level of Sca-1. The chemotherapy sensitivity to cisplatin of CXCR4(+) LLC was lower than that of CXCR4(-) LLC. The expression of ABCG2 and IGF1R mRNA in CXCR4(+) LLC was higher than that in CXCR4(-) LLC (P < 0.01). Most of CXCR4(+) LLC cells were close to vascular endothelial cells, aberrant vasculature around it was forming. The expression of VEGF and MMP9 mRNA in CXCR4(+) LLC was higher than that in CXCR4(-) LLC (P < 0.05), the microvessel density (MVD) of CXCR4(+) subsets growing were higher than that of CXCR4(-) subsets growing tumor tissue (P < 0.01). The tumor size, volume, and metastatic foci in the lungs of CXCR4(+) LLC was significantly higher than that in CXCR4(-) LLC (P < 0.001). Similarly, elevated expression of MMP9 and VEGF was also positively associated with CXCR4(+) LLC. Our results demonstrated that CXCR4(+) cells from Lewis lung carcinoma cell line exhibit cancer metastatic stem cell characteristics.
越来越多的证据表明，癌症干细胞有助于许多肿瘤的发生和发展。因此，为了在 Lewis 肺癌细胞系（LLC）中发现并鉴定转移性肿瘤干细胞样细胞，我们通过流式细胞术测量 LLC 中 CXCR4 的表达，并通过激光共聚焦显微镜（LSCM）观察。通过磁细胞分选从 LLC 中分离出 CXCR4（+）LLC 后，通过其致瘤和转移潜力来评估其特性。CXCR4（+）细胞占 LLC 总数的 0.18%，LSCM 鉴定免疫荧光染色细胞。在无血清培养基中培养的 CXCR4（+）LLC 悬浮细胞表达高水平的 Sca-1。CXCR4（+）LLC 对顺铂的化疗敏感性低于 CXCR4（-）LLC。CXCR4（+）LLC 中 ABCG2 和 IGF1R mRNA 的表达高于 CXCR4（-）LLC（P < 0.01）。大多数 CXCR4（+）LLC 细胞靠近血管内皮细胞，其周围形成异常的血管。CXCR4（+）LLC 中 VEGF 和 MMP9 mRNA 的表达高于 CXCR4（-）LLC（P < 0.05），CXCR4（+）亚群生长的微血管密度（MVD）高于 CXCR4（-）亚群生长的肿瘤组织（P < 0.01）。CXCR4（+）LLC 的肿瘤大小、体积和肺部转移灶明显高于 CXCR4（-）LLC（P < 0.001）。同样，MMP9 和 VEGF 的高表达也与 CXCR4（+）LLC 呈正相关。我们的研究结果表明，Lewis 肺癌细胞系中的 CXCR4（+）细胞具有癌症转移干细胞的特征。
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