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PRODUCTION METHOD FOR ARTIFICIAL CANCER STEM CELL AND INDUCED DIFFERENTIATION METHOD THEREFOR

外国特許コード F130007422
整理番号 S2011-0743-C0
掲載日 2013年6月20日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2012JP063302
国際公開番号 WO 2012165287
国際出願日 平成24年5月24日(2012.5.24)
国際公開日 平成24年12月6日(2012.12.6)
優先権データ
  • 特願2011-118557 (2011.5.27) JP
発明の名称 (英語) PRODUCTION METHOD FOR ARTIFICIAL CANCER STEM CELL AND INDUCED DIFFERENTIATION METHOD THEREFOR
発明の概要(英語) Provided are a cancer stem cell and a production method therefor. The production method for a multipotent cancer stem cell includes a step for introducing Oct3/4, Sox-2, Klf-4, and c-Myc genes into immortalized epithelial cells. A multipotent cancer stem cell produced by this method is provided.
従来技術、競合技術の概要(英語) BACKGROUND ART
Recent advances in stem cell biology studies, blood cancer and solid tumor cancer stem cells in the presence of strongly suggested. Solid cancer, a small subset of cancer stem cells (side population: also referred to as SP) is present, this population can be used in order to maintain the tumor mass, self-replicating exclusively by undifferentiated cancer stem cells that retain the ability while maintaining produce a number of cancer cells. Cancer stem cell-specific targeting it is possible to control factor, efficiently deplete cancer stem cells from the tumor may be. Such therapeutic agents can be developed, can be to cure cancer. However, such to identify the critical controlling factor, in cancer patient's tumor-derived cancer stem cells also gather, in addition, a portion of the cancer cell lines also gather, the fraction is not uniform, and the identification of cancer stem cell-specific inhibitor search cannot be performed. Therefore, it is possible to create pure 100% as long as the cancer stem cells, it is considered that greatly facilitated the study of the above.
The definition of cancer stem cells self-renewal, (1) pluripotency, (2) are implanted into immunodeficient mice the (3) same phenotype of the original cancer cancer forms are reduced. ' Cancer stem cells' term, ability to self-replicate (malignant tumor phenotype is split into a tumor cell populations in various fields as) defined for convenience as having cancer cells. Many tumors, that reproduce within the body, with tumorigenicity transformed into cancer stem cells derived from single cells. However, origins of cancer stem cells is still not known.
Cancer stem cells, on the basis of cell surface marker expression of various identified, tumor mass or from cancer cell lines can be collected using a cell sorter. However in this method a population of cancer stem cells collected and is a heteroatom, with the features of pure cancer stem cells and only a small part of cells, cancer stem cells in the strict cannot.
In solid tumors (SP) and specific sub-population, the nature of functional cancer stem cells has been achieved. It includes self-replicating and differentiation by raising the ability to form the entire tumor. Solid cancer cell populations in a cell having a specific cell surface marker of cancer stem cells by having known. For example, brain tumors (glioblastoma), prostate cancer, colon cancer, CD133 + cells and CD133 - cells separated from the these cancers of the immune-compromised mice to xenograft experiments, also, in the in vitro ability to self-replicate, growth, have the ability to differentiate from, and CD133 + cells is shown to be cancer stem cells (non-patent document 1-3). In addition, the expression of CD44 in breast cancer is high, a lower expression of the CD24 fractions (CD44 (- / low) CD24 (+) ) have the property of cancer stem cells (non-patent document 4) shown.
However, these cell surface markers of cancer stem cells relies on the separation of, cancer stem cells are separated from the 100% cannot be said to be, in addition, isolated cells in the maintenance or amplification is very difficult. Therefore, it is possible to create artificially cancer stem cells have been developed.
Miyoshi et al. recently, various cancer cells of the gastrointestinal system (cancer cell line) expressing reprogramming factors in cancer stem cells by the induction of successful (non-patent document 5) reports.
However, these cancer cell lines is already been transformed (malignancy, cancer) a number of genes and a mutation or a chromosomal abnormalities has been achieved. Therefore a homogenous cell population which is not configured, drug screening and biomarker considered not suitable for search. Therefore, the cells are defined as pure cancer stem cells is difficult.
On the other hand, human fibroblasts SOX2, OCT4, Klf4, c-Myc yamanaka et al. 4 of the two genes with a retroviral vector can be introduced, (Embryonic stem cells embryonic stem cells: cell ES) induced pluripotent stem cell similar to induce (induced pluripotent stem cell, iPS cell) (non-patent document 6) shown.
However, these 4 human genes introduced will not an immortalized cell, one of these 4 gene introduction, as well as the initialization of the cell, is simultaneously thereby causing cancer, human cancer stem cells are shown it to be formed is not reported.
  • 出願人(英語)
  • ※2012年7月以前掲載分については米国以外のすべての指定国
  • Public University Corporation Yokohama City University
  • 発明者(英語)
  • RYO, Akihide
  • NISHI, Mayuko
国際特許分類(IPC)
指定国 National States: AE AG AL AM AO AT AU AZ BA BB BG BH BR BW BY BZ CA CH CL CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IS JP KE KG KM KN KP KR KZ LA LC LK LR LS LT LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PE PG PH PL PT QA RO RS RU RW SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG
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