Department of Etiology and Carcinogenesis, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
Int J Oncol. 2012 Feb;40(2):370-7. doi: 10.3892/ijo.2011.1232. Epub 2011 Oct 13.
Prior studies on the biology and therapeutic application of human stem cells in human malignancies have reported mixed results. Some evidence shows the use of stem cell transplantation is an important tool in the treatment of several hematologic and non-hematologic malignancies while some others suggest both human stem cells and mature stromal cells can contribute to the development and growth of human malignancies. Aiming to provide more evidence on this controversial issue, we investigated the effect of cell fusion of mesenchymal stem cells with esophageal carcinoma cells on tumorigenesis. Results suggest that artificial fusion of human umbilical cord mesenchymal stem cells with esophageal carcinoma cells resulted in hybrids with declined cell growth, increased apoptosis and suppressed tumorigenicity. The comparison of gene expression profiles of human mesenchymal stem cells, esophageal carcinoma cells and hybrids indicated that fusion induced activation of apoptosis. Furthermore, the expression of DUSP6/MKP3 in MAPK pathway increased strikingly and the exogenous overexpression confirmed the growth suppression. Our results demonstrate fusion of human mesenchymal stem cells with esophageal carcinoma cells induced apoptosis and benign transdifferentiation rather than reprogramming to cancer stem cells.
先前关于人类干细胞在人类恶性肿瘤中的生物学和治疗应用的研究报告结果不一。一些证据表明，干细胞移植的使用是治疗几种血液系统和非血液系统恶性肿瘤的重要工具，而另一些证据则表明，人类干细胞和成熟基质细胞都可能有助于恶性肿瘤的发展和生长。为了提供更多关于这一争议性问题的证据，我们研究了间质干细胞与食管癌细胞融合对肿瘤发生的影响。结果表明，人脐带间充质干细胞与食管癌细胞的人工融合导致杂种细胞生长下降、凋亡增加和致瘤性受到抑制。人骨髓间充质干细胞、食管癌细胞和杂种细胞的基因表达谱比较表明，融合诱导了细胞凋亡的激活。此外，MAPK 通路中 DUSP6/MKP3 的表达显著增加，外源性过表达证实了生长抑制。我们的结果表明，人骨髓间充质干细胞与食管癌细胞的融合诱导了细胞凋亡和良性转分化，而不是向癌症干细胞重编程。
