Cadherin-11 regulates the metastasis of Ewing sarcoma cells to bone
Ewing sarcoma (ES) is a small round-cell tumor of the bones and soft tissues. ES frequently causes distant metastases, particularly in the lung and bone, which worsens patient prognosis. Cadherin-11 (Cad-11) is an adhesion molecule that is highly expressed in osteoblasts. Its expression is associate...
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| Veröffentlicht in: | Clinical & experimental metastasis 2015-08, Vol.32 (6), p.579-591 |
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| creator | Hatano, Mihoko Matsumoto, Yoshihiro Fukushi, Jun-ichi Matsunobu, Tomoya Endo, Makoto Okada, Seiji Iura, Kunio Kamura, Satoshi Fujiwara, Toshifumi Iida, Keiichiro Fujiwara, Yuko Nabeshima, Akira Yokoyama, Nobuhiko Fukushima, Suguru Oda, Yoshinao Iwamoto, Yukihide |
| description | Ewing sarcoma (ES) is a small round-cell tumor of the bones and soft tissues. ES frequently causes distant metastases, particularly in the lung and bone, which worsens patient prognosis. Cadherin-11 (Cad-11) is an adhesion molecule that is highly expressed in osteoblasts. Its expression is associated with bone metastases in prostate and breast cancer patients, and is known to occur in ES. Here we investigated the effects of Cad-11 on bone metastases of ES. Human ES cell lines RD-ES, SK-ES-1, SK-N-MC, and TC-71 cells were transduced with lentivirus containing Cad-11 shRNA or control shRNA (ES/Cad-11 and ES/Ctr). RD-ES and TC-71 were infected with a lentivirus luciferase vector. Adhesion assays were performed using these cells and recombinant Cad-11-Fc chimera or mouse osteoblast cell line MC3T3-E1. Cell motility was investigated via wound-healing assay. Intracardiac injection of RD-ES/Cad-11 and RD-ES/Ctr was used to create a mouse model of experimental bone metastasis. The association between Cad-11 expression and bone metastases and clinical prognosis in ES patients was analyzed by immunohistochemistry. We found knockdown of Cad-11 in ES cells resulted in reduced attachment ability and cell motility. In a mouse model of metastasis, RD-ES/Cad-11 cells caused fewer metastases than RD-ES/Ctr cells. The expression of Cad-11 in ES patients was significantly related to bone metastases (
P
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| doi_str_mv | 10.1007/s10585-015-9729-y |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1827920962</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3750462831</sourcerecordid><originalsourceid>FETCH-LOGICAL-c559t-f16cb950665790ff67c2dc72ee4ba65257f3f6e7b0136b04c6bbb894352598ca3</originalsourceid><addsrcrecordid>eNqFkUtLAzEUhYMotlZ_gBsZcOMmepOZvJZS6gMEN7oOSZppp8yjJjNI_72prSKCCBeyuN899-YchM4JXBMAcRMJMMkwEIaVoApvDtCYMJFjQQU_RGOgnGKQSo7QSYwrACiEkMdoRDkoygUZo-nUzJc-VC0mJAt-MdSm9zHrlz5rfG9iqipmXZnN3qt2kUUTXNeYzPm6TlSX2a71p-ioNHX0Z_t3gl7vZi_TB_z0fP84vX3CjjHV45JwZxUDzplQUJZcODp3gnpfWMMZZaLMS-6FBZJzC4Xj1lqpijy1lHQmn6Crne46dG-Dj71uqri9xLS-G6ImkgpFQXH6P8qTYSTZIxN6-QtddUNo00c-KckVFSJRZEe50MUYfKnXoWpM2GgCehuG3oWhUxh6G4bepJmLvfJgGz__nvhyPwF0B8TUahc-_Fj9p-oHCIaSsQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1697869277</pqid></control><display><type>article</type><title>Cadherin-11 regulates the metastasis of Ewing sarcoma cells to bone</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Hatano, Mihoko ; Matsumoto, Yoshihiro ; Fukushi, Jun-ichi ; Matsunobu, Tomoya ; Endo, Makoto ; Okada, Seiji ; Iura, Kunio ; Kamura, Satoshi ; Fujiwara, Toshifumi ; Iida, Keiichiro ; Fujiwara, Yuko ; Nabeshima, Akira ; Yokoyama, Nobuhiko ; Fukushima, Suguru ; Oda, Yoshinao ; Iwamoto, Yukihide</creator><creatorcontrib>Hatano, Mihoko ; Matsumoto, Yoshihiro ; Fukushi, Jun-ichi ; Matsunobu, Tomoya ; Endo, Makoto ; Okada, Seiji ; Iura, Kunio ; Kamura, Satoshi ; Fujiwara, Toshifumi ; Iida, Keiichiro ; Fujiwara, Yuko ; Nabeshima, Akira ; Yokoyama, Nobuhiko ; Fukushima, Suguru ; Oda, Yoshinao ; Iwamoto, Yukihide</creatorcontrib><description>Ewing sarcoma (ES) is a small round-cell tumor of the bones and soft tissues. ES frequently causes distant metastases, particularly in the lung and bone, which worsens patient prognosis. Cadherin-11 (Cad-11) is an adhesion molecule that is highly expressed in osteoblasts. Its expression is associated with bone metastases in prostate and breast cancer patients, and is known to occur in ES. Here we investigated the effects of Cad-11 on bone metastases of ES. Human ES cell lines RD-ES, SK-ES-1, SK-N-MC, and TC-71 cells were transduced with lentivirus containing Cad-11 shRNA or control shRNA (ES/Cad-11 and ES/Ctr). RD-ES and TC-71 were infected with a lentivirus luciferase vector. Adhesion assays were performed using these cells and recombinant Cad-11-Fc chimera or mouse osteoblast cell line MC3T3-E1. Cell motility was investigated via wound-healing assay. Intracardiac injection of RD-ES/Cad-11 and RD-ES/Ctr was used to create a mouse model of experimental bone metastasis. The association between Cad-11 expression and bone metastases and clinical prognosis in ES patients was analyzed by immunohistochemistry. We found knockdown of Cad-11 in ES cells resulted in reduced attachment ability and cell motility. In a mouse model of metastasis, RD-ES/Cad-11 cells caused fewer metastases than RD-ES/Ctr cells. The expression of Cad-11 in ES patients was significantly related to bone metastases (
P
< 0.05, logistic regression) and poorer overall survival (
P
< 0.05, log-rank test). These findings may explain that Cad-11 in ES cells may be essential for cell adhesion and motility, and is a promising molecular target for patients with ES.</description><identifier>ISSN: 0262-0898</identifier><identifier>EISSN: 1573-7276</identifier><identifier>DOI: 10.1007/s10585-015-9729-y</identifier><identifier>PMID: 26092671</identifier><identifier>CODEN: CEXMD2</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Animals ; Antibodies, Monoclonal - pharmacology ; Apoptosis ; Biomedical and Life Sciences ; Biomedicine ; Blotting, Western ; Bone Neoplasms - metabolism ; Bone Neoplasms - mortality ; Bone Neoplasms - secondary ; Cadherins - antagonists & inhibitors ; Cadherins - immunology ; Cadherins - metabolism ; Cancer Research ; Cell Adhesion ; Cell Movement ; Cell Proliferation ; Coculture Techniques ; Female ; Flow Cytometry ; Hematology ; Humans ; Immunoenzyme Techniques ; Lentivirus ; Luciferases - metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Staging ; Oncology ; Osteoblasts - metabolism ; Osteoblasts - pathology ; Prognosis ; Real-Time Polymerase Chain Reaction ; Research Paper ; Retroviridae ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; Sarcoma, Ewing - metabolism ; Sarcoma, Ewing - mortality ; Sarcoma, Ewing - pathology ; Surgical Oncology ; Survival Rate ; Tumor Cells, Cultured ; Wound Healing ; Xenograft Model Antitumor Assays</subject><ispartof>Clinical & experimental metastasis, 2015-08, Vol.32 (6), p.579-591</ispartof><rights>Springer Science+Business Media Dordrecht 2015</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c559t-f16cb950665790ff67c2dc72ee4ba65257f3f6e7b0136b04c6bbb894352598ca3</citedby><cites>FETCH-LOGICAL-c559t-f16cb950665790ff67c2dc72ee4ba65257f3f6e7b0136b04c6bbb894352598ca3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10585-015-9729-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10585-015-9729-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26092671$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hatano, Mihoko</creatorcontrib><creatorcontrib>Matsumoto, Yoshihiro</creatorcontrib><creatorcontrib>Fukushi, Jun-ichi</creatorcontrib><creatorcontrib>Matsunobu, Tomoya</creatorcontrib><creatorcontrib>Endo, Makoto</creatorcontrib><creatorcontrib>Okada, Seiji</creatorcontrib><creatorcontrib>Iura, Kunio</creatorcontrib><creatorcontrib>Kamura, Satoshi</creatorcontrib><creatorcontrib>Fujiwara, Toshifumi</creatorcontrib><creatorcontrib>Iida, Keiichiro</creatorcontrib><creatorcontrib>Fujiwara, Yuko</creatorcontrib><creatorcontrib>Nabeshima, Akira</creatorcontrib><creatorcontrib>Yokoyama, Nobuhiko</creatorcontrib><creatorcontrib>Fukushima, Suguru</creatorcontrib><creatorcontrib>Oda, Yoshinao</creatorcontrib><creatorcontrib>Iwamoto, Yukihide</creatorcontrib><title>Cadherin-11 regulates the metastasis of Ewing sarcoma cells to bone</title><title>Clinical & experimental metastasis</title><addtitle>Clin Exp Metastasis</addtitle><addtitle>Clin Exp Metastasis</addtitle><description>Ewing sarcoma (ES) is a small round-cell tumor of the bones and soft tissues. ES frequently causes distant metastases, particularly in the lung and bone, which worsens patient prognosis. Cadherin-11 (Cad-11) is an adhesion molecule that is highly expressed in osteoblasts. Its expression is associated with bone metastases in prostate and breast cancer patients, and is known to occur in ES. Here we investigated the effects of Cad-11 on bone metastases of ES. Human ES cell lines RD-ES, SK-ES-1, SK-N-MC, and TC-71 cells were transduced with lentivirus containing Cad-11 shRNA or control shRNA (ES/Cad-11 and ES/Ctr). RD-ES and TC-71 were infected with a lentivirus luciferase vector. Adhesion assays were performed using these cells and recombinant Cad-11-Fc chimera or mouse osteoblast cell line MC3T3-E1. Cell motility was investigated via wound-healing assay. Intracardiac injection of RD-ES/Cad-11 and RD-ES/Ctr was used to create a mouse model of experimental bone metastasis. The association between Cad-11 expression and bone metastases and clinical prognosis in ES patients was analyzed by immunohistochemistry. We found knockdown of Cad-11 in ES cells resulted in reduced attachment ability and cell motility. In a mouse model of metastasis, RD-ES/Cad-11 cells caused fewer metastases than RD-ES/Ctr cells. The expression of Cad-11 in ES patients was significantly related to bone metastases (
P
< 0.05, logistic regression) and poorer overall survival (
P
< 0.05, log-rank test). These findings may explain that Cad-11 in ES cells may be essential for cell adhesion and motility, and is a promising molecular target for patients with ES.</description><subject>Animals</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Apoptosis</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Blotting, Western</subject><subject>Bone Neoplasms - metabolism</subject><subject>Bone Neoplasms - mortality</subject><subject>Bone Neoplasms - secondary</subject><subject>Cadherins - antagonists & inhibitors</subject><subject>Cadherins - immunology</subject><subject>Cadherins - metabolism</subject><subject>Cancer Research</subject><subject>Cell Adhesion</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Coculture Techniques</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Hematology</subject><subject>Humans</subject><subject>Immunoenzyme Techniques</subject><subject>Lentivirus</subject><subject>Luciferases - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Neoplasm Staging</subject><subject>Oncology</subject><subject>Osteoblasts - metabolism</subject><subject>Osteoblasts - pathology</subject><subject>Prognosis</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Research Paper</subject><subject>Retroviridae</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>Sarcoma, Ewing - metabolism</subject><subject>Sarcoma, Ewing - mortality</subject><subject>Sarcoma, Ewing - pathology</subject><subject>Surgical Oncology</subject><subject>Survival Rate</subject><subject>Tumor Cells, Cultured</subject><subject>Wound Healing</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0262-0898</issn><issn>1573-7276</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkUtLAzEUhYMotlZ_gBsZcOMmepOZvJZS6gMEN7oOSZppp8yjJjNI_72prSKCCBeyuN899-YchM4JXBMAcRMJMMkwEIaVoApvDtCYMJFjQQU_RGOgnGKQSo7QSYwrACiEkMdoRDkoygUZo-nUzJc-VC0mJAt-MdSm9zHrlz5rfG9iqipmXZnN3qt2kUUTXNeYzPm6TlSX2a71p-ioNHX0Z_t3gl7vZi_TB_z0fP84vX3CjjHV45JwZxUDzplQUJZcODp3gnpfWMMZZaLMS-6FBZJzC4Xj1lqpijy1lHQmn6Crne46dG-Dj71uqri9xLS-G6ImkgpFQXH6P8qTYSTZIxN6-QtddUNo00c-KckVFSJRZEe50MUYfKnXoWpM2GgCehuG3oWhUxh6G4bepJmLvfJgGz__nvhyPwF0B8TUahc-_Fj9p-oHCIaSsQ</recordid><startdate>20150801</startdate><enddate>20150801</enddate><creator>Hatano, Mihoko</creator><creator>Matsumoto, Yoshihiro</creator><creator>Fukushi, Jun-ichi</creator><creator>Matsunobu, Tomoya</creator><creator>Endo, Makoto</creator><creator>Okada, Seiji</creator><creator>Iura, Kunio</creator><creator>Kamura, Satoshi</creator><creator>Fujiwara, Toshifumi</creator><creator>Iida, Keiichiro</creator><creator>Fujiwara, Yuko</creator><creator>Nabeshima, Akira</creator><creator>Yokoyama, Nobuhiko</creator><creator>Fukushima, Suguru</creator><creator>Oda, Yoshinao</creator><creator>Iwamoto, Yukihide</creator><general>Springer Netherlands</general><general>Springer Nature B.V</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>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FG</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>P5Z</scope><scope>P62</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>7QP</scope></search><sort><creationdate>20150801</creationdate><title>Cadherin-11 regulates the metastasis of Ewing sarcoma cells to bone</title><author>Hatano, Mihoko ; Matsumoto, Yoshihiro ; Fukushi, Jun-ichi ; Matsunobu, Tomoya ; Endo, Makoto ; Okada, Seiji ; Iura, Kunio ; Kamura, Satoshi ; Fujiwara, Toshifumi ; Iida, Keiichiro ; Fujiwara, Yuko ; Nabeshima, Akira ; Yokoyama, Nobuhiko ; Fukushima, Suguru ; Oda, Yoshinao ; Iwamoto, Yukihide</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c559t-f16cb950665790ff67c2dc72ee4ba65257f3f6e7b0136b04c6bbb894352598ca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Apoptosis</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Blotting, Western</topic><topic>Bone Neoplasms - metabolism</topic><topic>Bone Neoplasms - mortality</topic><topic>Bone Neoplasms - secondary</topic><topic>Cadherins - antagonists & inhibitors</topic><topic>Cadherins - immunology</topic><topic>Cadherins - metabolism</topic><topic>Cancer Research</topic><topic>Cell Adhesion</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Coculture Techniques</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Hematology</topic><topic>Humans</topic><topic>Immunoenzyme Techniques</topic><topic>Lentivirus</topic><topic>Luciferases - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Neoplasm Staging</topic><topic>Oncology</topic><topic>Osteoblasts - metabolism</topic><topic>Osteoblasts - pathology</topic><topic>Prognosis</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Research Paper</topic><topic>Retroviridae</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>Sarcoma, Ewing - metabolism</topic><topic>Sarcoma, Ewing - mortality</topic><topic>Sarcoma, Ewing - pathology</topic><topic>Surgical Oncology</topic><topic>Survival Rate</topic><topic>Tumor Cells, Cultured</topic><topic>Wound Healing</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hatano, Mihoko</creatorcontrib><creatorcontrib>Matsumoto, Yoshihiro</creatorcontrib><creatorcontrib>Fukushi, Jun-ichi</creatorcontrib><creatorcontrib>Matsunobu, Tomoya</creatorcontrib><creatorcontrib>Endo, Makoto</creatorcontrib><creatorcontrib>Okada, Seiji</creatorcontrib><creatorcontrib>Iura, Kunio</creatorcontrib><creatorcontrib>Kamura, Satoshi</creatorcontrib><creatorcontrib>Fujiwara, Toshifumi</creatorcontrib><creatorcontrib>Iida, Keiichiro</creatorcontrib><creatorcontrib>Fujiwara, Yuko</creatorcontrib><creatorcontrib>Nabeshima, Akira</creatorcontrib><creatorcontrib>Yokoyama, Nobuhiko</creatorcontrib><creatorcontrib>Fukushima, Suguru</creatorcontrib><creatorcontrib>Oda, Yoshinao</creatorcontrib><creatorcontrib>Iwamoto, Yukihide</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>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Advanced Technologies & Aerospace Collection</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</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>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>Calcium & Calcified Tissue Abstracts</collection><jtitle>Clinical & experimental metastasis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hatano, Mihoko</au><au>Matsumoto, Yoshihiro</au><au>Fukushi, Jun-ichi</au><au>Matsunobu, Tomoya</au><au>Endo, Makoto</au><au>Okada, Seiji</au><au>Iura, Kunio</au><au>Kamura, Satoshi</au><au>Fujiwara, Toshifumi</au><au>Iida, Keiichiro</au><au>Fujiwara, Yuko</au><au>Nabeshima, Akira</au><au>Yokoyama, Nobuhiko</au><au>Fukushima, Suguru</au><au>Oda, Yoshinao</au><au>Iwamoto, Yukihide</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cadherin-11 regulates the metastasis of Ewing sarcoma cells to bone</atitle><jtitle>Clinical & experimental metastasis</jtitle><stitle>Clin Exp Metastasis</stitle><addtitle>Clin Exp Metastasis</addtitle><date>2015-08-01</date><risdate>2015</risdate><volume>32</volume><issue>6</issue><spage>579</spage><epage>591</epage><pages>579-591</pages><issn>0262-0898</issn><eissn>1573-7276</eissn><coden>CEXMD2</coden><abstract>Ewing sarcoma (ES) is a small round-cell tumor of the bones and soft tissues. ES frequently causes distant metastases, particularly in the lung and bone, which worsens patient prognosis. Cadherin-11 (Cad-11) is an adhesion molecule that is highly expressed in osteoblasts. Its expression is associated with bone metastases in prostate and breast cancer patients, and is known to occur in ES. Here we investigated the effects of Cad-11 on bone metastases of ES. Human ES cell lines RD-ES, SK-ES-1, SK-N-MC, and TC-71 cells were transduced with lentivirus containing Cad-11 shRNA or control shRNA (ES/Cad-11 and ES/Ctr). RD-ES and TC-71 were infected with a lentivirus luciferase vector. Adhesion assays were performed using these cells and recombinant Cad-11-Fc chimera or mouse osteoblast cell line MC3T3-E1. Cell motility was investigated via wound-healing assay. Intracardiac injection of RD-ES/Cad-11 and RD-ES/Ctr was used to create a mouse model of experimental bone metastasis. The association between Cad-11 expression and bone metastases and clinical prognosis in ES patients was analyzed by immunohistochemistry. We found knockdown of Cad-11 in ES cells resulted in reduced attachment ability and cell motility. In a mouse model of metastasis, RD-ES/Cad-11 cells caused fewer metastases than RD-ES/Ctr cells. The expression of Cad-11 in ES patients was significantly related to bone metastases (
P
< 0.05, logistic regression) and poorer overall survival (
P
< 0.05, log-rank test). These findings may explain that Cad-11 in ES cells may be essential for cell adhesion and motility, and is a promising molecular target for patients with ES.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>26092671</pmid><doi>10.1007/s10585-015-9729-y</doi><tpages>13</tpages></addata></record> |
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| ispartof | Clinical & experimental metastasis, 2015-08, Vol.32 (6), p.579-591 |
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| subjects | Animals Antibodies, Monoclonal - pharmacology Apoptosis Biomedical and Life Sciences Biomedicine Blotting, Western Bone Neoplasms - metabolism Bone Neoplasms - mortality Bone Neoplasms - secondary Cadherins - antagonists & inhibitors Cadherins - immunology Cadherins - metabolism Cancer Research Cell Adhesion Cell Movement Cell Proliferation Coculture Techniques Female Flow Cytometry Hematology Humans Immunoenzyme Techniques Lentivirus Luciferases - metabolism Mice Mice, Inbred BALB C Mice, Nude Neoplasm Staging Oncology Osteoblasts - metabolism Osteoblasts - pathology Prognosis Real-Time Polymerase Chain Reaction Research Paper Retroviridae Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics Sarcoma, Ewing - metabolism Sarcoma, Ewing - mortality Sarcoma, Ewing - pathology Surgical Oncology Survival Rate Tumor Cells, Cultured Wound Healing Xenograft Model Antitumor Assays |
| title | Cadherin-11 regulates the metastasis of Ewing sarcoma cells to bone |
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