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Fusion with mesenchymal stem cells differentially affects tumorigenic and metastatic abilities of lung cancer cells
Author(s) -
Zhang LiNa,
Kong ChenFei,
Zhao Dan,
Cong XianLing,
Wang ShenSen,
Ma Ling,
Huang YingHui
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27011
Subject(s) - mesenchymal stem cell , cancer research , cancer stem cell , biology , lung cancer , stem cell , cell fusion , cancer cell , cancer , microbiology and biotechnology , cell culture , pathology , medicine , genetics
Cell fusion plays a crucial role in cancer progression and leads to massive aberrant changes in chromosome and gene expression involved in tumor metastasis. Cancer cells can fuse with many cell types, including stromal cells, epithelial cells, macrophages, and endothelial cells. Mesenchymal stem cells (MSCs) have been reported to migrate and incorporate into tumor sites during cancer progression. However, the underlying mechanism of stem cell fusion in tumor metastasis has not been fully deciphered. In this research, we established a cell fusion model between lung cancer cells and MSCs in vitro. We found that the hybrid cells showed enhanced metastatic capacity with increased expression of MMP‐2 and MMP‐9, whereas the proliferation ability was inhibited and cell cycle was blocked in the G 0 /G 1 phase with elevated expression of p21, p27, and p53. Moreover, the hybrid cells lost epithelial morphology and exhibited an epithelial‐mesenchymal transition (EMT) change with downregulation of E‐cadherin and upregulation of N‐cadherin, Vimentin, α‐SMA and Fibronectin1. Meanwhile, the expressions of EMT transcription factors, including Snail1, Slug, Twist1, Zeb1, and Zeb2, were also increased in hybrid cells. More important, the fusion hybrids acquired stem cell‐like properties, which exhibited increased expression stem cell transcription factors Oct4, Sox2, Nanog, Kif4 as well as Bmi1. Taken together, our results suggested that cell fusion between lung cancer cells and MSCs offered enhanced metastatic capacity and characteristics of cancer stem cell by undergoing EMT. This study will contribute to explaning the origin of lung cancer stem cells and to elucidate the role of cell fusion in cancer metastasis.