Side population of pancreatic cancer cells predominates in TGF‐β‐mediated epithelial to mesenchymal transition and invasion
We report here side population (SP) cells, a cancer stem cell enriched fraction from pancreatic cancer cell line, have enormous superior potential of the epithelial to mesenchymal transition (EMT), invasion, and metastasis. In an isolated SP cell culture, the cells rapidly expressed and up‐regulated...
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| Veröffentlicht in: | International journal of cancer 2009-06, Vol.124 (12), p.2771-2779 |
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| creator | Kabashima, Ayano Higuchi, Hajime Takaishi, Hiromasa Matsuzaki, Yumi Suzuki, Sadafumi Izumiya, Motoko Iizuka, Hideko Sakai, Gen Hozawa, Shigenari Azuma, Toshifumi Hibi, Toshifumi |
| description | We report here side population (SP) cells, a cancer stem cell enriched fraction from pancreatic cancer cell line, have enormous superior potential of the epithelial to mesenchymal transition (EMT), invasion, and metastasis. In an isolated SP cell culture, the cells rapidly expressed and up‐regulated E‐cadherin, an epithelial phenotypic marker, and the cells formed tightly contacted cell cluster, which is a representative epithelial phenotypic appearance. When the SP cells were incubated in the presence of TGF‐β, SP cells changed their shape into mesenchymal‐like appearance including spindle shaped assembly. This alteration was associated with significant reduction of E‐cadherin expression level. TGF‐β induced EMT‐associated gene alteration such as reduction of E‐cadherin mRNA and induction of Snail mRNA and matrixmetalloproteinase (MMP)‐2 mRNA. Finally, SP cells exerted notable matrigel invasion activity in response to TGF‐β treatment, whereas MP cells did not respond to TGF‐β‐mediated invasion. In conclusion, these results suggest that SP cells from pancreatic cancer cell line possess superior potentials of phenotypic switch, i.e., EMT/MET, micro‐invasion, and in vivo metastasis, as compared to MP cells. Because micro‐invasion and metastasis are key mechanisms of cancer malignant potential, SP cells would be the attractive target for preventing cancer progression. © 2008 UICC |
| doi_str_mv | 10.1002/ijc.24349 |
| format | Article |
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In an isolated SP cell culture, the cells rapidly expressed and up‐regulated E‐cadherin, an epithelial phenotypic marker, and the cells formed tightly contacted cell cluster, which is a representative epithelial phenotypic appearance. When the SP cells were incubated in the presence of TGF‐β, SP cells changed their shape into mesenchymal‐like appearance including spindle shaped assembly. This alteration was associated with significant reduction of E‐cadherin expression level. TGF‐β induced EMT‐associated gene alteration such as reduction of E‐cadherin mRNA and induction of Snail mRNA and matrixmetalloproteinase (MMP)‐2 mRNA. Finally, SP cells exerted notable matrigel invasion activity in response to TGF‐β treatment, whereas MP cells did not respond to TGF‐β‐mediated invasion. In conclusion, these results suggest that SP cells from pancreatic cancer cell line possess superior potentials of phenotypic switch, i.e., EMT/MET, micro‐invasion, and in vivo metastasis, as compared to MP cells. Because micro‐invasion and metastasis are key mechanisms of cancer malignant potential, SP cells would be the attractive target for preventing cancer progression. © 2008 UICC</description><identifier>ISSN: 0020-7136</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.24349</identifier><identifier>PMID: 19296540</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Animals ; Cadherins - genetics ; cancer stem cell ; Cell Line, Tumor ; Cell Transdifferentiation - drug effects ; Epithelial Cells - metabolism ; Epithelial Cells - pathology ; E‐cadherin ; Flow Cytometry ; Fluorescent Antibody Technique, Indirect ; Humans ; Immunoblotting ; invasion ; Liver Neoplasms - secondary ; Matrix Metalloproteinase 2 - genetics ; Mesoderm - metabolism ; Mesoderm - pathology ; metastasis ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Neoplasm Invasiveness ; Neoplastic Stem Cells - pathology ; Pancreatic Neoplasms - metabolism ; Pancreatic Neoplasms - pathology ; Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Snail Family Transcription Factors ; TGF‐beta ; Transcription Factors - genetics ; Transforming Growth Factor beta - pharmacology</subject><ispartof>International journal of cancer, 2009-06, Vol.124 (12), p.2771-2779</ispartof><rights>Copyright © 2009 UICC</rights><rights>Copyright 2008 UICC.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3589-ede77eef584795667197f07ed5700f55960556ccd5735cbfb9d4ad80145da6403</citedby><cites>FETCH-LOGICAL-c3589-ede77eef584795667197f07ed5700f55960556ccd5735cbfb9d4ad80145da6403</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fijc.24349$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fijc.24349$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19296540$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kabashima, Ayano</creatorcontrib><creatorcontrib>Higuchi, Hajime</creatorcontrib><creatorcontrib>Takaishi, Hiromasa</creatorcontrib><creatorcontrib>Matsuzaki, Yumi</creatorcontrib><creatorcontrib>Suzuki, Sadafumi</creatorcontrib><creatorcontrib>Izumiya, Motoko</creatorcontrib><creatorcontrib>Iizuka, Hideko</creatorcontrib><creatorcontrib>Sakai, Gen</creatorcontrib><creatorcontrib>Hozawa, Shigenari</creatorcontrib><creatorcontrib>Azuma, Toshifumi</creatorcontrib><creatorcontrib>Hibi, Toshifumi</creatorcontrib><title>Side population of pancreatic cancer cells predominates in TGF‐β‐mediated epithelial to mesenchymal transition and invasion</title><title>International journal of cancer</title><addtitle>Int J Cancer</addtitle><description>We report here side population (SP) cells, a cancer stem cell enriched fraction from pancreatic cancer cell line, have enormous superior potential of the epithelial to mesenchymal transition (EMT), invasion, and metastasis. In an isolated SP cell culture, the cells rapidly expressed and up‐regulated E‐cadherin, an epithelial phenotypic marker, and the cells formed tightly contacted cell cluster, which is a representative epithelial phenotypic appearance. When the SP cells were incubated in the presence of TGF‐β, SP cells changed their shape into mesenchymal‐like appearance including spindle shaped assembly. This alteration was associated with significant reduction of E‐cadherin expression level. TGF‐β induced EMT‐associated gene alteration such as reduction of E‐cadherin mRNA and induction of Snail mRNA and matrixmetalloproteinase (MMP)‐2 mRNA. Finally, SP cells exerted notable matrigel invasion activity in response to TGF‐β treatment, whereas MP cells did not respond to TGF‐β‐mediated invasion. In conclusion, these results suggest that SP cells from pancreatic cancer cell line possess superior potentials of phenotypic switch, i.e., EMT/MET, micro‐invasion, and in vivo metastasis, as compared to MP cells. Because micro‐invasion and metastasis are key mechanisms of cancer malignant potential, SP cells would be the attractive target for preventing cancer progression. © 2008 UICC</description><subject>Animals</subject><subject>Cadherins - genetics</subject><subject>cancer stem cell</subject><subject>Cell Line, Tumor</subject><subject>Cell Transdifferentiation - drug effects</subject><subject>Epithelial Cells - metabolism</subject><subject>Epithelial Cells - pathology</subject><subject>E‐cadherin</subject><subject>Flow Cytometry</subject><subject>Fluorescent Antibody Technique, Indirect</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>invasion</subject><subject>Liver Neoplasms - secondary</subject><subject>Matrix Metalloproteinase 2 - genetics</subject><subject>Mesoderm - metabolism</subject><subject>Mesoderm - pathology</subject><subject>metastasis</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Polymerase Chain Reaction</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Snail Family Transcription Factors</subject><subject>TGF‐beta</subject><subject>Transcription Factors - genetics</subject><subject>Transforming Growth Factor beta - pharmacology</subject><issn>0020-7136</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1OAyEYhonR2FpdeAHDysTF6EcHhrI0ja0aExfW9YTCN5Fm_oSpprsewbN4EA_hSaS2iSs3wAsPD-El5JTBJQMYXrmFuRzylKs90megZAJDJvZJP55BIlma9chRCAsAxgTwQ9JjaqgywaFP1k_OIm2bdlnqzjU1bQra6tp4jNFQE5foqcGyDLT1aJvK1brDQF1NZ9PJ9_rj6zMOFVoXty3F1nUvWDpd0q6hFQaszcuq2kSv6-B-39C1jfffdIjhmBwUugx4spsH5HlyMxvfJg-P07vx9UNiUjFSCVqUErEQIy6VyDLJlCxAohUSoBBCZSBEZkzMqTDzYq4s13YEjAurMw7pgJxvva1vXpcYurxyYfMvXWOzDHk0ppLxNIIXW9D4JgSPRd56V2m_yhnkm7rzWHf-W3dkz3bS5TxW8Efu-o3A1RZ4dyWu_jfld_fjrfIH9lmOJA</recordid><startdate>20090615</startdate><enddate>20090615</enddate><creator>Kabashima, Ayano</creator><creator>Higuchi, Hajime</creator><creator>Takaishi, Hiromasa</creator><creator>Matsuzaki, Yumi</creator><creator>Suzuki, Sadafumi</creator><creator>Izumiya, Motoko</creator><creator>Iizuka, Hideko</creator><creator>Sakai, Gen</creator><creator>Hozawa, Shigenari</creator><creator>Azuma, Toshifumi</creator><creator>Hibi, Toshifumi</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><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>7X8</scope></search><sort><creationdate>20090615</creationdate><title>Side population of pancreatic cancer cells predominates in TGF‐β‐mediated epithelial to mesenchymal transition and invasion</title><author>Kabashima, Ayano ; Higuchi, Hajime ; Takaishi, Hiromasa ; Matsuzaki, Yumi ; Suzuki, Sadafumi ; Izumiya, Motoko ; Iizuka, Hideko ; Sakai, Gen ; Hozawa, Shigenari ; Azuma, Toshifumi ; Hibi, Toshifumi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3589-ede77eef584795667197f07ed5700f55960556ccd5735cbfb9d4ad80145da6403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Cadherins - genetics</topic><topic>cancer stem cell</topic><topic>Cell Line, Tumor</topic><topic>Cell Transdifferentiation - drug effects</topic><topic>Epithelial Cells - metabolism</topic><topic>Epithelial Cells - pathology</topic><topic>E‐cadherin</topic><topic>Flow Cytometry</topic><topic>Fluorescent Antibody Technique, Indirect</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>invasion</topic><topic>Liver Neoplasms - secondary</topic><topic>Matrix Metalloproteinase 2 - genetics</topic><topic>Mesoderm - metabolism</topic><topic>Mesoderm - pathology</topic><topic>metastasis</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, SCID</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplastic Stem Cells - pathology</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Polymerase Chain Reaction</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Snail Family Transcription Factors</topic><topic>TGF‐beta</topic><topic>Transcription Factors - genetics</topic><topic>Transforming Growth Factor beta - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kabashima, Ayano</creatorcontrib><creatorcontrib>Higuchi, Hajime</creatorcontrib><creatorcontrib>Takaishi, Hiromasa</creatorcontrib><creatorcontrib>Matsuzaki, Yumi</creatorcontrib><creatorcontrib>Suzuki, Sadafumi</creatorcontrib><creatorcontrib>Izumiya, Motoko</creatorcontrib><creatorcontrib>Iizuka, Hideko</creatorcontrib><creatorcontrib>Sakai, Gen</creatorcontrib><creatorcontrib>Hozawa, Shigenari</creatorcontrib><creatorcontrib>Azuma, Toshifumi</creatorcontrib><creatorcontrib>Hibi, Toshifumi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kabashima, Ayano</au><au>Higuchi, Hajime</au><au>Takaishi, Hiromasa</au><au>Matsuzaki, Yumi</au><au>Suzuki, Sadafumi</au><au>Izumiya, Motoko</au><au>Iizuka, Hideko</au><au>Sakai, Gen</au><au>Hozawa, Shigenari</au><au>Azuma, Toshifumi</au><au>Hibi, Toshifumi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Side population of pancreatic cancer cells predominates in TGF‐β‐mediated epithelial to mesenchymal transition and invasion</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int J Cancer</addtitle><date>2009-06-15</date><risdate>2009</risdate><volume>124</volume><issue>12</issue><spage>2771</spage><epage>2779</epage><pages>2771-2779</pages><issn>0020-7136</issn><eissn>1097-0215</eissn><abstract>We report here side population (SP) cells, a cancer stem cell enriched fraction from pancreatic cancer cell line, have enormous superior potential of the epithelial to mesenchymal transition (EMT), invasion, and metastasis. In an isolated SP cell culture, the cells rapidly expressed and up‐regulated E‐cadherin, an epithelial phenotypic marker, and the cells formed tightly contacted cell cluster, which is a representative epithelial phenotypic appearance. When the SP cells were incubated in the presence of TGF‐β, SP cells changed their shape into mesenchymal‐like appearance including spindle shaped assembly. This alteration was associated with significant reduction of E‐cadherin expression level. TGF‐β induced EMT‐associated gene alteration such as reduction of E‐cadherin mRNA and induction of Snail mRNA and matrixmetalloproteinase (MMP)‐2 mRNA. Finally, SP cells exerted notable matrigel invasion activity in response to TGF‐β treatment, whereas MP cells did not respond to TGF‐β‐mediated invasion. In conclusion, these results suggest that SP cells from pancreatic cancer cell line possess superior potentials of phenotypic switch, i.e., EMT/MET, micro‐invasion, and in vivo metastasis, as compared to MP cells. Because micro‐invasion and metastasis are key mechanisms of cancer malignant potential, SP cells would be the attractive target for preventing cancer progression. © 2008 UICC</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>19296540</pmid><doi>10.1002/ijc.24349</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Cadherins - genetics cancer stem cell Cell Line, Tumor Cell Transdifferentiation - drug effects Epithelial Cells - metabolism Epithelial Cells - pathology E‐cadherin Flow Cytometry Fluorescent Antibody Technique, Indirect Humans Immunoblotting invasion Liver Neoplasms - secondary Matrix Metalloproteinase 2 - genetics Mesoderm - metabolism Mesoderm - pathology metastasis Mice Mice, Inbred NOD Mice, SCID Neoplasm Invasiveness Neoplastic Stem Cells - pathology Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - pathology Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics RNA, Messenger - metabolism Snail Family Transcription Factors TGF‐beta Transcription Factors - genetics Transforming Growth Factor beta - pharmacology |
| title | Side population of pancreatic cancer cells predominates in TGF‐β‐mediated epithelial to mesenchymal transition and invasion |
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