Mouse induced pluripotent stem cell microenvironment generates epithelial-mesenchymal transition in mouse Lewis lung cancer cells.
Induced pluripotent stem (iPS) cells may be a powerful tool in regenerative medicine, but their potential tumorigenicity is a significant challenge for the clinical use of iPS cells. Previously, we succeeded in converting miPS cells into cancer stem cells (CSCs) under the conditions of tumor microenvironment. Both stem cells and tumor cells are profoundly influenced by bi-directional communication with their respective microenvironment, which dictates cell fate determination and behavior. The microenvironment derived from iPS cells has not been well studied. In this paper, we have investigated the effects of secreted factors from Nanog-mouse iPS (miPS) cells on mouse Lewis lung cancer (LLC) cells that are found in the conditioned media. The results demonstrated that miPS cells secrete factors that can convert the epithelia phenotype of LLC cells to a mesenchymal phenotype, and that can promote tumorigenisity, migration and invasion. Furthermore, LLC cells that have been exposed to miPS conditioned medium became resistant to apoptosis. These various biological effects suggest that the miPS microenvironment contain factors that can promote an epithelial-mesenchymal transition (EMT) through an active Snail-MMP axis or by suppressing differentiation in LLC cells.
Department of Medical and Bioengineering Science, Graduate School of Natural Science and Technology, Okayama University Okayama 700-8530, Japan ; Department of Pathology, Tianjin Central Hospital of Gynecology Obstetrics Tianjin 300100, People's Republic of China ; Japan Society for The Promotion of Science Tokyo 102-8472, Japan.
Ling
L
Chen
Department of Medical and Bioengineering Science, Graduate School of Natural Science and Technology, Okayama University Okayama 700-8530, Japan.
Akifumi
A
Mizutani
Department of Medical and Bioengineering Science, Graduate School of Natural Science and Technology, Okayama University Okayama 700-8530, Japan.
Tomonari
T
Kasai
Department of Medical and Bioengineering Science, Graduate School of Natural Science and Technology, Okayama University Okayama 700-8530, Japan.
Ting
T
Yan
Department of Medical and Bioengineering Science, Graduate School of Natural Science and Technology, Okayama University Okayama 700-8530, Japan.
Guoliang
G
Jin
Department of Medical and Bioengineering Science, Graduate School of Natural Science and Technology, Okayama University Okayama 700-8530, Japan.
Arun
A
Vaidyanath
Department of Chemistry, Biochemistry Specialty, Faculty of Science, Menofia University Egypt.
Bishoy Ya
BY
El-Aarag
Japan Society for The Promotion of Science Tokyo 102-8472, Japan.
Yixin
Y
Liu
Department of Medical and Bioengineering Science, Graduate School of Natural Science and Technology, Okayama University Okayama 700-8530, Japan.
Takayuki
T
Kudoh
Mouse Cancer Genetics Program, Bldg 560, Room 12-67, National Cancer Institute, National Institutes of Health Frederick, MD 21702, USA.
David S
DS
Salomon
Department of Breast Cancer Pathology and Research Laboratory, State Key Laboratory of Breast Cancer Research, Cancer Hospital of Tianjin Medical University Tianjin 300060, People's Republic of China.
Li
L
Fu
Department of Medical and Bioengineering Science, Graduate School of Natural Science and Technology, Okayama University Okayama 700-8530, Japan.
Masaharu
M
Seno
Mouse induced pluripotent stem cell; epithelial-mesenchymal transition; lung Lewis cancer cell; stem cell microenvironment