{"corpus_id":21754500,"paper_sha":"53913bb9da86d89e1a213f26dfec2124907add9e","doi":"10.1016/j.canlet.2018.05.014","arxiv_id":null,"pmid":29775627,"pmcid":null,"mag_id":2803361288,"dblp_id":null,"acl_id":null,"title":"Acquisition of tumorigenic potential and therapeutic resistance in CD133+ subpopulation of prostate cancer cells exhibiting stem-cell like characteristics.","year":2018,"publication_date":"2018-08-01","venue":"Cancer Letters","journal":{"name":"Cancer letters","pages":"\n          25-33\n        ","volume":"430"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, N.I.H., Extramural","Research Support, U.S. Gov't, Non-P.H.S."],"s2_fields_of_study":["Biology","Medicine"],"reference_count":54,"citation_count":54,"influential_citation_count":2,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"AC133 Antigen","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D000071916"},{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Antineoplastic Agents","mj":false,"qs":[{"q":"pharmacology","mj":false,"ui":"Q000494"},{"q":"therapeutic use","mj":false,"ui":"Q000627"}],"ui":"D000970"},{"d":"Biomarkers, Tumor","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D014408"},{"d":"Carcinogenesis","mj":false,"qs":[{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D063646"},{"d":"Cell Line, Tumor","mj":false,"ui":"D045744"},{"d":"Core Binding Factor Alpha 1 Subunit","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D050659"},{"d":"Docetaxel","mj":false,"qs":[{"q":"pharmacology","mj":false,"ui":"Q000494"},{"q":"therapeutic use","mj":false,"ui":"Q000627"}],"ui":"D000077143"},{"d":"Drug Resistance, Neoplasm","mj":false,"ui":"D019008"},{"d":"Gene Expression Profiling","mj":false,"ui":"D020869"},{"d":"Gene Knockdown Techniques","mj":false,"ui":"D055785"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Mice","mj":false,"ui":"D051379"},{"d":"Mice, Inbred NOD","mj":false,"ui":"D016688"},{"d":"Mice, SCID","mj":false,"ui":"D016513"},{"d":"Neoplastic Stem Cells","mj":false,"qs":[{"q":"pathology","mj":true,"ui":"Q000473"}],"ui":"D014411"},{"d":"Prostatic Neoplasms","mj":false,"qs":[{"q":"pathology","mj":true,"ui":"Q000473"},{"q":"therapy","mj":false,"ui":"Q000628"}],"ui":"D011471"},{"d":"Radiation Tolerance","mj":false,"ui":"D011836"},{"d":"Up-Regulation","mj":false,"ui":"D015854"},{"d":"Xenograft Model Antitumor Assays","mj":false,"ui":"D023041"}],"chemicals":[{"n":"AC133 Antigen","ui":"D000071916","reg":"0"},{"n":"Antineoplastic Agents","ui":"D000970","reg":"0"},{"n":"Biomarkers, Tumor","ui":"D014408","reg":"0"},{"n":"Core Binding Factor Alpha 1 Subunit","ui":"D050659","reg":"0"},{"n":"PROM1 protein, human","ui":"C000606023","reg":"0"},{"n":"RUNX2 protein, human","ui":"C493709","reg":"0"},{"n":"Docetaxel","ui":"D000077143","reg":"15H5577CQD"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"http://manuscript.elsevier.com/S0304383518303392/pdf/S0304383518303392.pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/53913bb9da86d89e1a213f26dfec2124907add9e","s2_open_access_license":"publisher-specific-oa","s2_open_access_status":"BRONZE","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"The role of CD133 (Prominin-1) as a cancer stem cell marker may be useful for therapeutic approaches and prognostication in prostate cancer patients. We investigated the stem-cell-related function and biological features of a subpopulation of CD133+ cells isolated from established primary human prostate cancer cell lines. The CD133+ cells sorted from human prostate cancer 22Rv1 exhibited high clonogenic and tumorigenic capabilities, sphere forming capacity and serially reinitiated transplantable tumors in NOD-SCID mice. Gene profiling analysis of CD133+ cells showed upregulation of markers of stem cell differentiation (CD44, Oct4, SOX9 and Nanog), epithelial-to-mesenchymal transition (c-myc and BMI1), osteoblastic differentiation (Runx2), and skeletal morphogenesis (BMP2), compared to side population of CD133- cells. These cells are highly malignant and resistant to γ-radiation and chemotherapeutic drug, docetaxel. Importantly, a docetaxel-resistant subclone was more enriched in CD133+ cells with significant increase in Runx2 expression, compared to CD133- cells. Furthermore, knockdown of Runx2 in these cells resulted in differential response to chemotherapy, sensitizing them to increased cell death. These results demonstrate therapy-resistant population with stem-like features are distinct subpopulation of malignant cells that resides within parental cell lines. The molecular signature of CD133+ cells may lead to identification of novel therapeutic targets and prognostic markers in the treatment of prostate cancer.","claims":[{"public_id":"cl_02d46ade10d2073f7888b9cd688d0baa","status":"active","text":"A docetaxel-resistant subclone is more enriched in CD133+ cells and shows significantly increased Runx2 expression compared with CD133- cells.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_02d46ade10d2073f7888b9cd688d0baa"},{"public_id":"cl_abf6412b1793df87f98a90e9eb74039c","status":"active","text":"CD133+ cells are highly malignant and resistant to γ-radiation and docetaxel.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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mice.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_1cee88df1fd04bacfd3f625341e8fba9"},{"public_id":"cl_007aadaf56f356387037a747cb513bbf","status":"active","text":"Runx2 knockdown sensitizes these cells to chemotherapy and increases cell death.","confidence":0.96,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_007aadaf56f356387037a747cb513bbf"}],"concepts":[{"public_id":"co_024f8a4d3ce9f8f1c00e1ab1137fd6dd","status":"active","name":"cell death","description":"Loss of cell viability measured after Runx2 knockdown and chemotherapy exposure.","types":["outcome"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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