Development And Characterization Of Cancer Stem Cell Model From Mouse Ips Cells

The cancer stem cells in capable of continuous proliferation and self-renewal are proposed to play significant roles in oncogenesis, tumor growth, metastasis and cancer recurrence. Cancer stem cells are considered derived from normal stem cells affected by the tumor microenvironment although the mechanism of development is not clear yet. In 2007, Yamanaka9s group succeeded in generating Nanog mouse induced pluripotent stem (iPS) cells, in which green fluorescent protein has been inserted into the 5′ untranslated region of the Nanog gene. Usually, iPS cells are considered to be induced into progenitor cells, which differentiate into various normal phenotypes depending on the normal niche. We hypothesized that cancer stem cells could be derived from Nanog mouse iPS cells in the conditioned culture medium of cancer cell lines, which is a mimic of carcinoma microenvironment. As a result, the cells exhibited a high tumorigenicity in vivo with a capacity of self-renewal and the expression of markers associated with stem cell properties and an undifferentiated state. The cells efficiently formed spheroids expressing green fluorescent protein in suspension culture, vasculogenic tubes in MatriGel in vitro and exhibited extensive angiogenesis in vivo, which was confirmed by magnetic resonance imaging and by histochemical analysis. Thus we concluded that a model of cancer stem cells was originally developed using mouse iPS cells and proposed the conditioned culture medium might perform as niche for producing cancer stem cells. It is worthwhile noticing that the mouse iPS cells co-cultured with cancer-derived cells did not form malignant tumors in vivo. This implies that cell-to-cell contact may have inhibitory effect on the conversion of mouse iPS cells into cancer stem cells. Furthermore, demonstration of the genetic alterations and the secreted factors in the tumor microenvironment which convert mouse iPS cells to cancer stem cells, and identification of potentially bona fide markers of cancer stem cells will help the development of novel anti-cancer therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 418. doi:1538-7445.AM2012-418