Adhesion-Induced Drug Resistance in Leukemia Stem Cells
The co-culture of TF-1 leukemia cells and MS-5 stromal cells produces a cobblestone area which partially mimics the leukemia stem cell niche. The adhering leukemia cells are shown to become less sensitive to cytarabine, etoposide and daunorubicin. These changes are associated with an increased propo...
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| Veröffentlicht in: | Pharmacology 2010-01, Vol.86 (2), p.79-84 |
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| creator | Funayama, Keiji Murai, Fumihiko Shimane, Miyuki Nomura, Hitoshi Asano, Shigetaka |
| description | The co-culture of TF-1 leukemia cells and MS-5 stromal cells produces a cobblestone area which partially mimics the leukemia stem cell niche. The adhering leukemia cells are shown to become less sensitive to cytarabine, etoposide and daunorubicin. These changes are associated with an increased proportion of the G0/G1 phase, increased upregulation of cyclin-dependent kinase inhibitors, and increased levels of Bcl-2, but not with any change in the expression of BAX or drug transporters such as ABCG2 and MDR1, compared to monocultured leukemic cells. In addition, we demonstrate using a bioimaging technique that daunorubicin accumulates in the lysosomes of the adherent leukemic cells and that V-ATPase is activated. These findings suggest that adhesion alone can lead to drug resistance in leukemic stem cells by various mechanisms. |
| doi_str_mv | 10.1159/000305344 |
| format | Article |
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The adhering leukemia cells are shown to become less sensitive to cytarabine, etoposide and daunorubicin. These changes are associated with an increased proportion of the G0/G1 phase, increased upregulation of cyclin-dependent kinase inhibitors, and increased levels of Bcl-2, but not with any change in the expression of BAX or drug transporters such as ABCG2 and MDR1, compared to monocultured leukemic cells. In addition, we demonstrate using a bioimaging technique that daunorubicin accumulates in the lysosomes of the adherent leukemic cells and that V-ATPase is activated. These findings suggest that adhesion alone can lead to drug resistance in leukemic stem cells by various mechanisms.</description><identifier>ISSN: 0031-7012</identifier><identifier>EISSN: 1423-0313</identifier><identifier>DOI: 10.1159/000305344</identifier><identifier>PMID: 20689339</identifier><language>eng</language><publisher>Basel, Switzerland: S. 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Karger AG, Basel</rights><rights>Copyright 2010 S. Karger AG, Basel.</rights><rights>Copyright (c) 2010 S. Karger AG, Basel</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c333t-36672e75956ee0e82ee660224348b2ff77c66d73e78a9dc7e909457ddc642dc73</citedby><cites>FETCH-LOGICAL-c333t-36672e75956ee0e82ee660224348b2ff77c66d73e78a9dc7e909457ddc642dc73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,2430,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20689339$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Funayama, Keiji</creatorcontrib><creatorcontrib>Murai, Fumihiko</creatorcontrib><creatorcontrib>Shimane, Miyuki</creatorcontrib><creatorcontrib>Nomura, Hitoshi</creatorcontrib><creatorcontrib>Asano, Shigetaka</creatorcontrib><title>Adhesion-Induced Drug Resistance in Leukemia Stem Cells</title><title>Pharmacology</title><addtitle>Pharmacology</addtitle><description>The co-culture of TF-1 leukemia cells and MS-5 stromal cells produces a cobblestone area which partially mimics the leukemia stem cell niche. The adhering leukemia cells are shown to become less sensitive to cytarabine, etoposide and daunorubicin. These changes are associated with an increased proportion of the G0/G1 phase, increased upregulation of cyclin-dependent kinase inhibitors, and increased levels of Bcl-2, but not with any change in the expression of BAX or drug transporters such as ABCG2 and MDR1, compared to monocultured leukemic cells. In addition, we demonstrate using a bioimaging technique that daunorubicin accumulates in the lysosomes of the adherent leukemic cells and that V-ATPase is activated. These findings suggest that adhesion alone can lead to drug resistance in leukemic stem cells by various mechanisms.</description><subject>Antineoplastic Agents - pharmacokinetics</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Bone Marrow Cells - physiology</subject><subject>Cell Adhesion</subject><subject>Cell Cycle</subject><subject>Cell Line, Tumor</subject><subject>Coculture Techniques</subject><subject>Cyclin-Dependent Kinase Inhibitor Proteins - genetics</subject><subject>Cyclin-Dependent Kinase Inhibitor Proteins - metabolism</subject><subject>Cytarabine - pharmacology</subject><subject>Daunorubicin - pharmacokinetics</subject><subject>Daunorubicin - pharmacology</subject><subject>Drug Resistance, Neoplasm</subject><subject>Etoposide - pharmacology</subject><subject>Humans</subject><subject>Leukemia - metabolism</subject><subject>Leukemia - pathology</subject><subject>Leukemia - physiopathology</subject><subject>Lysosomes - metabolism</subject><subject>Neoplastic Stem Cells - drug effects</subject><subject>Neoplastic Stem Cells - physiology</subject><subject>Original Paper</subject><subject>Osmolar Concentration</subject><subject>Proto-Oncogene Proteins c-bcl-2 - genetics</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Stem Cell Niche - physiopathology</subject><subject>Stromal Cells - physiology</subject><subject>Up-Regulation</subject><subject>Vacuolar Proton-Translocating ATPases - genetics</subject><subject>Vacuolar Proton-Translocating ATPases - metabolism</subject><issn>0031-7012</issn><issn>1423-0313</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpd0EtLw0AQB_BFFFurB-8iAQ_iIbq7s9nHsdRXoSD4OId0d1LTNonuJge_vVtae_A0zPCbYfgTcs7oLWOZuaOUAs1AiAMyZIJDSoHBIRnGMUsVZXxATkJYRia50sdkwKnUBsAMiRq7TwxV26TTxvUWXXLv-0XyGmehKxqLSdUkM-xXWFdF8tZhnUxwvQ6n5Kgs1gHPdnVEPh4f3ifP6ezlaToZz1ILAF0KUiqOKjOZRKSoOaKUlHMBQs95WSplpXQKUOnCOKvQUCMy5ZyVgsceRuR6e_fLt989hi6vq2DjB0WDbR9yJQxlApiO8uqfXLa9b-JzOaOaSaO43qibrbK-DcFjmX_5qi78T0T5Jsx8H2a0l7uL_bxGt5d_6UVwsQWrwi_Q78Fu_xeHmHRd</recordid><startdate>20100101</startdate><enddate>20100101</enddate><creator>Funayama, Keiji</creator><creator>Murai, Fumihiko</creator><creator>Shimane, Miyuki</creator><creator>Nomura, Hitoshi</creator><creator>Asano, Shigetaka</creator><general>S. 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pharmacokinetics</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Bone Marrow Cells - physiology</topic><topic>Cell Adhesion</topic><topic>Cell Cycle</topic><topic>Cell Line, Tumor</topic><topic>Coculture Techniques</topic><topic>Cyclin-Dependent Kinase Inhibitor Proteins - genetics</topic><topic>Cyclin-Dependent Kinase Inhibitor Proteins - metabolism</topic><topic>Cytarabine - pharmacology</topic><topic>Daunorubicin - pharmacokinetics</topic><topic>Daunorubicin - pharmacology</topic><topic>Drug Resistance, Neoplasm</topic><topic>Etoposide - pharmacology</topic><topic>Humans</topic><topic>Leukemia - metabolism</topic><topic>Leukemia - pathology</topic><topic>Leukemia - physiopathology</topic><topic>Lysosomes - metabolism</topic><topic>Neoplastic Stem Cells - drug effects</topic><topic>Neoplastic Stem Cells - physiology</topic><topic>Original Paper</topic><topic>Osmolar Concentration</topic><topic>Proto-Oncogene Proteins c-bcl-2 - genetics</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><topic>Stem Cell Niche - physiopathology</topic><topic>Stromal Cells - physiology</topic><topic>Up-Regulation</topic><topic>Vacuolar Proton-Translocating ATPases - genetics</topic><topic>Vacuolar Proton-Translocating ATPases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Funayama, Keiji</creatorcontrib><creatorcontrib>Murai, Fumihiko</creatorcontrib><creatorcontrib>Shimane, Miyuki</creatorcontrib><creatorcontrib>Nomura, Hitoshi</creatorcontrib><creatorcontrib>Asano, Shigetaka</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Proquest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - 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The adhering leukemia cells are shown to become less sensitive to cytarabine, etoposide and daunorubicin. These changes are associated with an increased proportion of the G0/G1 phase, increased upregulation of cyclin-dependent kinase inhibitors, and increased levels of Bcl-2, but not with any change in the expression of BAX or drug transporters such as ABCG2 and MDR1, compared to monocultured leukemic cells. In addition, we demonstrate using a bioimaging technique that daunorubicin accumulates in the lysosomes of the adherent leukemic cells and that V-ATPase is activated. These findings suggest that adhesion alone can lead to drug resistance in leukemic stem cells by various mechanisms.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>20689339</pmid><doi>10.1159/000305344</doi><tpages>6</tpages></addata></record> |
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| ispartof | Pharmacology, 2010-01, Vol.86 (2), p.79-84 |
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| language | eng |
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| source | MEDLINE; Karger Journals; Alma/SFX Local Collection |
| subjects | Antineoplastic Agents - pharmacokinetics Antineoplastic Agents - pharmacology Bone Marrow Cells - physiology Cell Adhesion Cell Cycle Cell Line, Tumor Coculture Techniques Cyclin-Dependent Kinase Inhibitor Proteins - genetics Cyclin-Dependent Kinase Inhibitor Proteins - metabolism Cytarabine - pharmacology Daunorubicin - pharmacokinetics Daunorubicin - pharmacology Drug Resistance, Neoplasm Etoposide - pharmacology Humans Leukemia - metabolism Leukemia - pathology Leukemia - physiopathology Lysosomes - metabolism Neoplastic Stem Cells - drug effects Neoplastic Stem Cells - physiology Original Paper Osmolar Concentration Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-bcl-2 - metabolism Stem Cell Niche - physiopathology Stromal Cells - physiology Up-Regulation Vacuolar Proton-Translocating ATPases - genetics Vacuolar Proton-Translocating ATPases - metabolism |
| title | Adhesion-Induced Drug Resistance in Leukemia Stem Cells |
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