title: Characterization of cancer stem-like cells derived from mouse induced pluripotent stem cells transformed by tumor-derived extracellular vesicles.
abstract: Several studies have shown that cancer niche can perform an active role in the regulation of tumor cell maintenance and progression through extracellular vesicles-based intercellular communication. However, it has not been reported whether this vesicle-mediated communication affects the malignant transformation of normal stem cells/progenitors. We have previously reported that the conditioned medium derived from the mouse Lewis Lung Carcinoma (LLC) cell line can convert mouse induced pluripotent stem cells (miPSCs) into cancer stem cells (CSCs), indicating that normal stem cells when placed in an aberrant microenvironment can give rise to functionally active CSCs. Here, we focused on the contribution of tumor-derived extracellular vesicles (tEVs) that are secreted from LLC cells to induce the transformation of miPSCs into CSCs. We isolated tEVs from the conditioned medium of LLC cells, and then the differentiating miPSCs were exposed to tEVs for 4 weeks. The resultant tEV treated cells (miPS-LLCev) expressed Nanog and Oct3/4 proteins comparable to miPSCs. The frequency of sphere formation of the miPS-LLCev cells in suspension culture indicated that the self-renewal capacity of the miPS-LLCev cells was significant. When the miPS-LLCev cells were subcutaneously transplanted into Balb/c nude mice, malignant liposarcomas with extensive angiogenesis developed. miPS-LLCevPT and miPS-LLCevDT, the cells established from primary site and disseminated liposarcomas, respectively, showed their capacities to self-renew and differentiate into adipocytes and endothelial cells. Moreover, we confirmed the secondary liposarcoma development when these cells were transplanted. Taken together, these results indicate that miPS-LLCev cells possess CSC properties. Thus, our current study provides the first evidence that tEVs have the potential to induce CSC properties in normal tissue stem cells/progenitors.
authors: 1. Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3.1.1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
authors: Ting
authors: T
authors: Yan
authors: 1. Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3.1.1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
authors: Akifumi
authors: A
authors: Mizutani
authors: 2. Department of Pathology, Tianjin Central Hospital of Gynecology Obstetrics, No. 156, Sanmalu, Nankai District, Tianjin, 300100, China.
authors: Ling
authors: L
authors: Chen
authors: 1. Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3.1.1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
authors: Mai
authors: M
authors: Takaki
authors: 1. Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3.1.1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
authors: Yuki
authors: Y
authors: Hiramoto
authors: 1. Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3.1.1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
authors: Shuichi
authors: S
authors: Matsuda
authors: 1. Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3.1.1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
authors: Tsukasa
authors: T
authors: Shigehiro
authors: 1. Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3.1.1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
authors: Tomonari
authors: T
authors: Kasai
authors: 1. Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3.1.1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
authors: Takayuki
authors: T
authors: Kudoh
authors: 1. Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3.1.1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
authors: Hiroshi
authors: H
authors: Murakami
authors: 1. Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3.1.1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
authors: Junko
authors: J
authors: Masuda
authors: 3. Lurie Children's Research Center, Feinberg School of Medicine, Northwestern University, 2300 Children's Plaza, Box 222, Chicago, IL 60614-3394, USA.
authors: Mary J C
authors: MJ
authors: Hendrix
authors: 3. Lurie Children's Research Center, Feinberg School of Medicine, Northwestern University, 2300 Children's Plaza, Box 222, Chicago, IL 60614-3394, USA.
authors: Luigi
authors: L
authors: Strizzi
authors: 4. Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 2702, USA.
authors: David S
authors: DS
authors: Salomon
authors: 5. State Key Laboratory of Breast Cancer Research, Department of Breast Cancer Pathology and Research Laboratory, Cancer Hospital of Tianjin Medical University, Tianjin, China.
authors: Li
authors: L
authors: Fu
authors: 1. Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3.1.1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan.
authors: Masaharu
authors: M
authors: Seno
keywords: cancer stem cells; cancerous niche; extracellular vesicles; liposarcoma.; mouse induced pluripotent stem cells