| dc.description.abstract | Cancer-initiating cells or cancer stem cells (CSCs) exhibit a self-renewing capacity and are responsible for tumor generation. CSCs are stem cells that form tumors and exhibit stem cell properties, such as self-renewal and the ability to differentiate into multiple cell types. It was suggested that CSCs persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors. The development of specific therapies targeted at CSCs may improve the survival rates and the quality of life of cancer patients, particularly those suffering from metastatic disease. Several markers for colon CSCs have been proposed: CD24, CD29, CD44, CD133, CD166, Lgr5, Muc2, ESA, Msi-1, and ALDH-1. However, specific and reliable surface markers of colon CSCs have not been identified. The only reliable method to identify and quantify CSCs is the observation of tumor generation in the serial xenotransplantation model. In this study, the Colo205 and LoVo colon cancer cell lines and colon cancer cells established from the cells of colon cancer patients (Primary-colon cancer cells 0317) were cultured on ECM (nanosegment)-grafted, oligopeptide (nanosegment)-grafted, and Pluronic (nanosegment)-grafted dishes having different elasticity (100 kPa to 16 MPa elasticity) as well as tissue culture dishes (TCPS, 10GPa elasticity). The oligopeptide-grafted dishes were prepared from polyvinylalcohol-co-itaconic acid (PVA-IA) coating dishes grafted with several nanosegments (KGGPQVTRGDVFTMP [cell-binding domain derived from vitronectin, oligoVN], GGNGEPRGDTYRAY [cell-binding domain from bone sialoprotein, oligoBSP], and GKKQRFRHRNRKG [heparin-binding domain, oligoHBD]). We evaluated whether the CSCs were enhanced (purified) or decreased (depleted) among the colon cancer cells after the colon cancer cells were cultured on ECM-grafted, oligopeptide-grafted, TCPS, or Pluronic-grafted dishes. The ratio of the CSCs was evaluated from the tumor generation of cancer cells in mice that were subcutaneously xenotransplanted into mice. CSCs in colon cancer cells could be selectively depleted from colon cancer cells (Colo205, LoVo, and Primary-colon cancer cells) when they were cultured on Pluronic-grafted dishes having optimal elasticity, whereas CSCs were maintained on TCPS and extracellular matrix (ECM)-immobilized dishes as well as oligopeptide-immobilized dishes. Furthermore, there is no tumor generation of colon cancer cells cultured on pluronic-grafted dishes while there is tumor generation of colon cancer cells cultured on oligopeptide-immobilized dishes. On the other hand, anticancer drug (5-Fluorouracil) was used as well to identify CSCs in colon cancer cells. The results show the same tendency in in vitro cultivation and in vivo experiment. It was concluded that the pluronic-grafted dishes deplete cancer-initiating cells (CSCs) from colon cancer cells while CSCs in colon cancer cells remain or enhance on TCPS and oligopeptide-immobilized dishes, which was explained by specific biomedical characteristics of Pluronic. | en_US |