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CELL CULTURE SUBSTRATE, CANCER CELL AGGREGATE AND METHOD FOR MANUFACTURING SAME USING SAID SUBSTRATE, AND DRUG SCREENING METHOD USING SAID CANCER CELL AGGREGATE NEW

外国特許コード F180009554
整理番号 (S2017-0598-N0)
掲載日 2018年11月2日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2018JP014119
国際公開番号 WO 2018182044
国際出願日 平成30年4月2日(2018.4.2)
国際公開日 平成30年10月4日(2018.10.4)
優先権データ
  • 特願2017-072512 (2017.3.31) JP
発明の名称 (英語) CELL CULTURE SUBSTRATE, CANCER CELL AGGREGATE AND METHOD FOR MANUFACTURING SAME USING SAID SUBSTRATE, AND DRUG SCREENING METHOD USING SAID CANCER CELL AGGREGATE NEW
発明の概要(英語) [Problem] An objective of the present invention is the in-vitro production of a cancer cell population retaining native biological properties, such as morphological polarity and tissue motion polarity, of the original cancer tissue.
[Solution] The present invention pertains to a cell culture substrate comprising a base material and a biocompatible polymer layer, the cell culture substrate having, at prescribed intervals on the substrate surface, a plurality of rough sections having a prescribed surface structure having a prescribed shape and not covered by the biocompatibile polymer layer. The present invention makes it possible to use a very simple process, namely culturing cancer cells on a cell culture substrate having a prescribed structure, to obtain, in a living state, a cancer cell aggregate having the same morphological polarity and tissue motion polarity as is observed in-vivo, whereby the heretofore impossible live imaging of micro tumors in-vitro is made possible. Since it is considered that said cancer cell aggregate would reproduce the in-vivo sequence of cancer development, proliferation, invasion, metastasis and recurrence, the cancer cell aggregate could be used as a research tool for cancer research or for screening cancer drugs.
従来技術、競合技術の概要(英語) BACKGROUND ART
Cancer, still cannot completely overcome one of the disease.That the increase of the cost of drug development, and super senior involved in the increase of the number of cancer patients resulting in an increase in medical costs, a national financial has been a factor to strangle the.In such a situation, effective and inexpensive development of cancer therapeutic agents of the next generation, it is assumed that urgent problem.
In the study of cancer diseases, biological properties at the cellular level has been solved can be said that the progress of the other hand, a number of cancer cells is formed on the biological level of cancerous tissue kinetics characteristics, observed by the absence of the art processes, in spite of the importance are not of interest, as a result most of the not yet been elucidated.Therefore, the target cancerous tissue in vitro and the molecular basis of the physiological examination, in particular cancerous tissue as to elucidate the characteristics of the biological dynamics is, in the development of cancer therapeutic agents of the next generation, have a significant expected.
Cancer research has been carried out in conventional molecular level cancer tissue physiological considerations, primarily, ex vivo biological tissue sample was extracted and was observed with the pathological diagnosis, in the above embodiment can be estimated.On the other hand, a population of cancer cells in vitro in vivo live imaging technology, the technical difficulty and therefore has not been developed, the pathophysiological dynamics of the cancer tissue is rarely considered that it is not, a new anti-cancer agent or basic research of cancer development is performed, in the current.
Many epithelial system in cancer cells, invasion, metastasis (epithelial mesenchymal transformation) the EMT must be known.Epithelial carcinoma cancer cell system loses traits by the EMT system, such as invasive potential and capable of being in motion and acquire mesenchymal transformation invasion, metastasis and is considered to be the cause, recent studies have pancreatic ductal adenocarcinoma cells in the EMT does not require invasion, metastasis was found to occur (non-patent document 1).Not through the EMT a new cancer invasion, cell population as a transformation and movement (collective cell migration) of interest, the observed in vitro in vivo cancer cell population is a need for a technique has been increasingly in demand.
In vitro, a two-dimensional conventional single layer 2 is not in cell culture, to mimic the in vivo environment as more, has a special structure using a two-dimensional cell culture substrate 3 to form a mass, a so-called three-dimensional culture of cells 3 have been reported (for example Patent Document 1, such as 2).However, the three-dimensional cell culture 3 are formed by most of the cell mass, vigorous motion and the polarity of the polarity of the inflatable does not show morphological spheroids growth (spheroid mass of cancer cells) and, as a feature of the malignant tumor of the cancer cells in vivo in the invasive growth reflecting the population of the present invention is far.
In addition, normal epithelial cell growth and survival of the scaffold such as adhesion to the extracellular matrix is essential, cannot be adequately adhered to the scaffold (anoikis) epithelial cells are apoptotic anoikis referred to as the die.On the other hand, causes a cancer cell is EMT epitheliaf system, resistant to anoikis subject to cell death, the floating vessel from other tissue and metastasize HCCs are known.
Cancer epithelial cancer cell infiltration of anoikis-resistance, and easiness of transition from the involved, epithelial cancer cells to determine the resistance of the system the meaning of anoikis is large.However, a culture of epithelial cancer cells in the conventional system can be directed to the cell culture, the presence or absence of cancer cells are epithelial system regardless of anoikis resistance since adhesive, anoikis epithelial cancer cells in vitro to evaluate the resistance of the system is difficult.
  • 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
  • NATIONAL UNIVERSITY CORPORATION HOKKAIDO UNIVERSITY
  • 発明者(英語)
  • MIYATAKE YUKIKO
  • SHIGETOMI KAORI
  • OKAJIMA TAKAHARU
  • KASAHARA MASANORI
国際特許分類(IPC)
指定国 National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DJ DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JO JP KE KG KH KN KP KR KW KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA 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 KM ML MR NE SN ST TD TG
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