Tumor-Initiating Cells of Various Tumor Types Exhibit Differential Angiogenic Properties and React Differently to Antiangiogenic Drugs
Tumor‐initiating cells (TICs) are a subtype of tumor cells believed to be critical for initiating tumorigenesis. We sought to determine the angiogenic properties of TICs in different tumor types including U‐87MG (glioblastoma), HT29 (colon), MCF7 (breast), A549 (non‐small‐cell lung), and PANC1 (panc...
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| Veröffentlicht in: | Stem cells (Dayton, Ohio) Ohio), 2012-09, Vol.30 (9), p.1831-1841 |
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| creator | Benayoun, Liat Gingis-Velitski, Svetlana Voloshin, Tali Segal, Ehud Segev, Rotem Munster, Michal Bril, Rotem Satchi-Fainaro, Ronit Scherer, Stefan J. Shaked, Yuval |
| description | Tumor‐initiating cells (TICs) are a subtype of tumor cells believed to be critical for initiating tumorigenesis. We sought to determine the angiogenic properties of TICs in different tumor types including U‐87MG (glioblastoma), HT29 (colon), MCF7 (breast), A549 (non‐small‐cell lung), and PANC1 (pancreatic) cancers. Long‐term cultures grown either as monolayers (“TIC‐low”) or as nonadherent tumor spheres (“TIC‐high”) were generated. The TIC‐high fractions exhibited increased expression of stem cell surface markers, high aldehyde dehydrogenase activity, high expression of p21, and resistance to standard chemotherapy in comparison to TIC‐low fractions. Furthermore, TICs from U‐87MG and HT29 but not from MCF7, A549, and PANC1 tumor types possess increased angiogenic activity. Consequently, the efficacy of vascular endothelial growth factor‐A (VEGF‐A) neutralizing antibody is limited only to those tumors that are dependent on VEGF‐A activity. In addition, such therapy had little or reversed antiangiogenic effects on tumors that do not necessarily rely on VEGF‐dependent angiogenesis. Differential angiogenic activity and antiangiogenic therapy sensitivity were also observed in TICs of the same tumor type, suggesting redundant angiogenic pathways. Collectively, our results suggest that the efficacy of antiangiogenic drugs is dependent on the angiogenic properties of TICs and, therefore, can serve as a possible biomarker to predict antiangiogenic treatment efficacy. Stem Cells2012;30:1831–1841 |
| doi_str_mv | 10.1002/stem.1170 |
| format | Article |
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We sought to determine the angiogenic properties of TICs in different tumor types including U‐87MG (glioblastoma), HT29 (colon), MCF7 (breast), A549 (non‐small‐cell lung), and PANC1 (pancreatic) cancers. Long‐term cultures grown either as monolayers (“TIC‐low”) or as nonadherent tumor spheres (“TIC‐high”) were generated. The TIC‐high fractions exhibited increased expression of stem cell surface markers, high aldehyde dehydrogenase activity, high expression of p21, and resistance to standard chemotherapy in comparison to TIC‐low fractions. Furthermore, TICs from U‐87MG and HT29 but not from MCF7, A549, and PANC1 tumor types possess increased angiogenic activity. Consequently, the efficacy of vascular endothelial growth factor‐A (VEGF‐A) neutralizing antibody is limited only to those tumors that are dependent on VEGF‐A activity. In addition, such therapy had little or reversed antiangiogenic effects on tumors that do not necessarily rely on VEGF‐dependent angiogenesis. Differential angiogenic activity and antiangiogenic therapy sensitivity were also observed in TICs of the same tumor type, suggesting redundant angiogenic pathways. Collectively, our results suggest that the efficacy of antiangiogenic drugs is dependent on the angiogenic properties of TICs and, therefore, can serve as a possible biomarker to predict antiangiogenic treatment efficacy. Stem Cells2012;30:1831–1841</description><identifier>ISSN: 1066-5099</identifier><identifier>EISSN: 1549-4918</identifier><identifier>DOI: 10.1002/stem.1170</identifier><identifier>PMID: 22782858</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Angiogenesis ; Angiogenesis Inhibitors - pharmacology ; Animals ; Bone marrow-derived cells ; Cancer stem cells ; Cell Line, Tumor ; Cell Survival - drug effects ; Chemotherapy ; Disease Models, Animal ; HT29 Cells ; Human Umbilical Vein Endothelial Cells - drug effects ; Human Umbilical Vein Endothelial Cells - pathology ; Humans ; Immunoblotting ; MCF-7 Cells ; Medical research ; Mice ; Mice, Nude ; Neoplasms - blood supply ; Neoplasms - drug therapy ; Neoplasms - pathology ; Neoplastic Stem Cells - drug effects ; Neoplastic Stem Cells - metabolism ; Neoplastic Stem Cells - pathology ; Neovascularization, Pathologic - drug therapy ; Neovascularization, Pathologic - pathology ; Transfection ; Transplantation, Heterologous ; Tumors ; Vascular endothelial growth factor</subject><ispartof>Stem cells (Dayton, Ohio), 2012-09, Vol.30 (9), p.1831-1841</ispartof><rights>Copyright © 2012 AlphaMed Press</rights><rights>Copyright © 2012 AlphaMed Press.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4260-174b4f6dc8b2918c0b6538516a60840491f4b182b09d508c6b51194bdba23eaf3</citedby><cites>FETCH-LOGICAL-c4260-174b4f6dc8b2918c0b6538516a60840491f4b182b09d508c6b51194bdba23eaf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22782858$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Benayoun, Liat</creatorcontrib><creatorcontrib>Gingis-Velitski, Svetlana</creatorcontrib><creatorcontrib>Voloshin, Tali</creatorcontrib><creatorcontrib>Segal, Ehud</creatorcontrib><creatorcontrib>Segev, Rotem</creatorcontrib><creatorcontrib>Munster, Michal</creatorcontrib><creatorcontrib>Bril, Rotem</creatorcontrib><creatorcontrib>Satchi-Fainaro, Ronit</creatorcontrib><creatorcontrib>Scherer, Stefan J.</creatorcontrib><creatorcontrib>Shaked, Yuval</creatorcontrib><title>Tumor-Initiating Cells of Various Tumor Types Exhibit Differential Angiogenic Properties and React Differently to Antiangiogenic Drugs</title><title>Stem cells (Dayton, Ohio)</title><addtitle>STEM CELLS</addtitle><description>Tumor‐initiating cells (TICs) are a subtype of tumor cells believed to be critical for initiating tumorigenesis. We sought to determine the angiogenic properties of TICs in different tumor types including U‐87MG (glioblastoma), HT29 (colon), MCF7 (breast), A549 (non‐small‐cell lung), and PANC1 (pancreatic) cancers. Long‐term cultures grown either as monolayers (“TIC‐low”) or as nonadherent tumor spheres (“TIC‐high”) were generated. The TIC‐high fractions exhibited increased expression of stem cell surface markers, high aldehyde dehydrogenase activity, high expression of p21, and resistance to standard chemotherapy in comparison to TIC‐low fractions. Furthermore, TICs from U‐87MG and HT29 but not from MCF7, A549, and PANC1 tumor types possess increased angiogenic activity. Consequently, the efficacy of vascular endothelial growth factor‐A (VEGF‐A) neutralizing antibody is limited only to those tumors that are dependent on VEGF‐A activity. In addition, such therapy had little or reversed antiangiogenic effects on tumors that do not necessarily rely on VEGF‐dependent angiogenesis. Differential angiogenic activity and antiangiogenic therapy sensitivity were also observed in TICs of the same tumor type, suggesting redundant angiogenic pathways. Collectively, our results suggest that the efficacy of antiangiogenic drugs is dependent on the angiogenic properties of TICs and, therefore, can serve as a possible biomarker to predict antiangiogenic treatment efficacy. Stem Cells2012;30:1831–1841</description><subject>Angiogenesis</subject><subject>Angiogenesis Inhibitors - pharmacology</subject><subject>Animals</subject><subject>Bone marrow-derived cells</subject><subject>Cancer stem cells</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Chemotherapy</subject><subject>Disease Models, Animal</subject><subject>HT29 Cells</subject><subject>Human Umbilical Vein Endothelial Cells - drug effects</subject><subject>Human Umbilical Vein Endothelial Cells - pathology</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>MCF-7 Cells</subject><subject>Medical research</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Neoplasms - blood supply</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - pathology</subject><subject>Neoplastic Stem Cells - drug effects</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Neovascularization, Pathologic - drug therapy</subject><subject>Neovascularization, Pathologic - pathology</subject><subject>Transfection</subject><subject>Transplantation, Heterologous</subject><subject>Tumors</subject><subject>Vascular endothelial growth factor</subject><issn>1066-5099</issn><issn>1549-4918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kdFu0zAYhS3ExMbGBS-ALHEDF9n8O7bjXI6utJMGg67ApWUnTvFI4mInYn0BnnsuLQMhcWVL_r4jHx2EngM5BULoWRxsdwpQkEfoCDgrM1aCfJzuRIiMk7I8RE9jvCUEGJfyCTqktJBUcnmEfi7HzofssneD04PrV3hi2zZi3-DPOjg_RvyLwMvN2kY8vfvqjBvwhWsaG2yfpBaf9yvnV7Z3Ff4Q_NqGwSVU9zVeWF39BbcbPPiEJ-uPchHGVTxBB41uo322P4_Rp7fT5WSeXV3PLifnV1nFqCAZFMywRtSVNDRVrIgRPJcchBZEMpJqN8yApIaUNSeyEoYDlMzURtPc6iY_Rq92uevgv482DqpzsUqNdW9TVwUkZ4KXnPOEvvwHvfVj6NPvFABwKgSIMlGvd1QVfIzBNmodXKfDJkWp7ThqO47ajpPYF_vE0XS2fiB_r5GAsx3ww7V28_8kdbOcvttHZjvDpce7B0OHb0oUecHVl_cz9XG-mC_e3CzULL8HuBqpcA</recordid><startdate>201209</startdate><enddate>201209</enddate><creator>Benayoun, Liat</creator><creator>Gingis-Velitski, Svetlana</creator><creator>Voloshin, Tali</creator><creator>Segal, Ehud</creator><creator>Segev, Rotem</creator><creator>Munster, Michal</creator><creator>Bril, Rotem</creator><creator>Satchi-Fainaro, Ronit</creator><creator>Scherer, Stefan J.</creator><creator>Shaked, Yuval</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Oxford University Press</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201209</creationdate><title>Tumor-Initiating Cells of Various Tumor Types Exhibit Differential Angiogenic Properties and React Differently to Antiangiogenic Drugs</title><author>Benayoun, Liat ; 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We sought to determine the angiogenic properties of TICs in different tumor types including U‐87MG (glioblastoma), HT29 (colon), MCF7 (breast), A549 (non‐small‐cell lung), and PANC1 (pancreatic) cancers. Long‐term cultures grown either as monolayers (“TIC‐low”) or as nonadherent tumor spheres (“TIC‐high”) were generated. The TIC‐high fractions exhibited increased expression of stem cell surface markers, high aldehyde dehydrogenase activity, high expression of p21, and resistance to standard chemotherapy in comparison to TIC‐low fractions. Furthermore, TICs from U‐87MG and HT29 but not from MCF7, A549, and PANC1 tumor types possess increased angiogenic activity. Consequently, the efficacy of vascular endothelial growth factor‐A (VEGF‐A) neutralizing antibody is limited only to those tumors that are dependent on VEGF‐A activity. In addition, such therapy had little or reversed antiangiogenic effects on tumors that do not necessarily rely on VEGF‐dependent angiogenesis. Differential angiogenic activity and antiangiogenic therapy sensitivity were also observed in TICs of the same tumor type, suggesting redundant angiogenic pathways. Collectively, our results suggest that the efficacy of antiangiogenic drugs is dependent on the angiogenic properties of TICs and, therefore, can serve as a possible biomarker to predict antiangiogenic treatment efficacy. Stem Cells2012;30:1831–1841</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>22782858</pmid><doi>10.1002/stem.1170</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Angiogenesis Angiogenesis Inhibitors - pharmacology Animals Bone marrow-derived cells Cancer stem cells Cell Line, Tumor Cell Survival - drug effects Chemotherapy Disease Models, Animal HT29 Cells Human Umbilical Vein Endothelial Cells - drug effects Human Umbilical Vein Endothelial Cells - pathology Humans Immunoblotting MCF-7 Cells Medical research Mice Mice, Nude Neoplasms - blood supply Neoplasms - drug therapy Neoplasms - pathology Neoplastic Stem Cells - drug effects Neoplastic Stem Cells - metabolism Neoplastic Stem Cells - pathology Neovascularization, Pathologic - drug therapy Neovascularization, Pathologic - pathology Transfection Transplantation, Heterologous Tumors Vascular endothelial growth factor |
| title | Tumor-Initiating Cells of Various Tumor Types Exhibit Differential Angiogenic Properties and React Differently to Antiangiogenic Drugs |
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