Chen Yue, Jiang Tinghui, Mao Aiwu, Xu Jianrong
Department of Radiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai, 200127, China.
Tumour Biol. 2014 Dec;35(12):12749-55. doi: 10.1007/s13277-014-2601-x. Epub 2014 Sep 12.
Cancer stem cells (CSCs) are a distinct population in tumors and cause cancer relapse and metastasis. Thus, treating CSCs are believed to be potential to cure rapidly growing and highly metastatic cancers. To date, CSCs in esophageal cancer have not been characterized. In the current study, we detected significant higher levels of placental growth factor (PLGF) and matrix metalloproteinase 9 (MMP9) in the esophageal cancers with metastasis, compared to those without metastasis, in which the expression levels of PLGF and MMP9 strongly correlated with each other. Thus, we used a human esophageal cancer cell line, TE-1, to examine the cross talk of PLGF and MMP9. We found that the levels of PLGF in TE-1 cells positively affected the levels of MMP9, while the levels of MMP9 did not affected the levels of PLGF, suggesting that PLGF may activate MMP9 in esophageal cancer cells. Then, we separated PLGF-positive and PLGF-negative TE-1 cells that had been transfected with a GFP reporter under a PLGF promoter by flow cytometry. We found that PLGF-positive cells grew significantly faster than PLGF-negative cells both in vitro and in vivo in a stereotactical implantation model, suggesting that PLGF-positive cells are likely CSCs in esophageal cancer. Taken together, we demonstrate that PLGF-positive cells appear to be CSCs in esophageal cancer, and they may release PLGF to promote cancer metastasis through MMP9 activation.
癌症干细胞（CSCs）是肿瘤中的一个独特群体，可导致癌症复发和转移。因此，治疗癌症干细胞被认为有治愈快速生长和高转移性癌症的潜力。迄今为止，食管癌中的癌症干细胞尚未得到鉴定。在本研究中，我们检测到与无转移的食管癌相比，有转移的食管癌中胎盘生长因子（PLGF）和基质金属蛋白酶9（MMP9）水平显著更高，其中PLGF和MMP9的表达水平彼此密切相关。因此，我们使用人食管癌细胞系TE-1来研究PLGF和MMP9之间的相互作用。我们发现TE-1细胞中PLGF的水平对MMP9的水平有正向影响，而MMP9的水平对PLGF的水平没有影响，这表明PLGF可能在食管癌细胞中激活MMP9。然后，我们通过流式细胞术分离出在PLGF启动子下转染了绿色荧光蛋白（GFP）报告基因的PLGF阳性和PLGF阴性TE-1细胞。我们发现，在立体定向植入模型中，PLGF阳性细胞在体外和体内的生长速度均显著快于PLGF阴性细胞，这表明PLGF阳性细胞可能是食管癌中的癌症干细胞。综上所述，我们证明PLGF阳性细胞似乎是食管癌中的癌症干细胞，它们可能通过激活MMP9释放PLGF以促进癌症转移。
