Netrin-4 overexpression suppresses primary and metastatic colorectal tumor progression
Tumor angiogenesis is closely associated with clinical staging and has been proposed to correlate with clinical response in terms of subsequent metastases following primary resection. Netrin-4 (NT-4) regulates angiogenic responses. Therefore, we sought to examine the effects of NT-4 on the primary t...
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| Veröffentlicht in: | Oncology reports 2013-01, Vol.29 (1), p.73-78 |
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| creator | EVENO, CLARISSE CONTRERES, JEAN-OLIVIER HAINAUD, PATRICIA NEMETH, JUDITH DUPUY, EVELYNE POCARD, MARC |
| description | Tumor angiogenesis is closely associated with clinical staging and has been proposed to correlate with clinical response in terms of subsequent metastases following primary resection. Netrin-4 (NT-4) regulates angiogenic responses. Therefore, we sought to examine the effects of NT-4 on the primary tumor growth of colon cancer cells, liver and lung metastases of colon cancer cells, and responses following primary tumor resection. We used 3 different mouse models of orthotopic primary tumor and liver and lung metastases, comparing 2 human colon cancer cells lines: wild-type (low expression of NT-4) and NT-4 (overexpression of NT-4) LS174 cells. NT-4 overexpression inhibited the primary tumor growth of colorectal LS174 xenografts in nude mice (144.3±12.9 vs. 62.4±4.5 mm3; P |
| doi_str_mv | 10.3892/or.2012.2104 |
| format | Article |
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Netrin-4 (NT-4) regulates angiogenic responses. Therefore, we sought to examine the effects of NT-4 on the primary tumor growth of colon cancer cells, liver and lung metastases of colon cancer cells, and responses following primary tumor resection. We used 3 different mouse models of orthotopic primary tumor and liver and lung metastases, comparing 2 human colon cancer cells lines: wild-type (low expression of NT-4) and NT-4 (overexpression of NT-4) LS174 cells. NT-4 overexpression inhibited the primary tumor growth of colorectal LS174 xenografts in nude mice (144.3±12.9 vs. 62.4±4.5 mm3; P<0.0001) as well as its related local and systemic recurrence (38 vs. 0%; P<0.01). NT-4 overexpression also markedly decreased colorectal cancer progression in terms of tumor number and volume of liver metastases in the NT-4 group of the orthotopic liver metastasis model (25 vs. 90% and 4±1 vs. 709±190 mm3, P<0.001 and P<0.05). Collectively, our findings indicate that NT-4 overexpression decreases colorectal lung metastasis and its associated lymph node involvement. NT-4 overexpression decreases tumor recurrence and metastasis after surgical resection, likely via an anti-angiogenic effect. These observations suggest that NT-4 may hold therapeutic potential in the treatment of colorectal cancer growth and major metastatic sites.</description><identifier>ISSN: 1021-335X</identifier><identifier>EISSN: 1791-2431</identifier><identifier>DOI: 10.3892/or.2012.2104</identifier><identifier>PMID: 23124703</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Angiogenesis ; Animals ; Apoptosis ; Cancer therapies ; Cell growth ; colon cancer ; Colonic Neoplasms - metabolism ; Colonic Neoplasms - pathology ; Colonic Neoplasms - prevention & control ; Colorectal cancer ; Disease Progression ; Female ; Humans ; Laboratory animals ; liver metastasis ; Liver Neoplasms - metabolism ; Liver Neoplasms - prevention & control ; Liver Neoplasms - secondary ; Lung Neoplasms - metabolism ; Lung Neoplasms - prevention & control ; Lung Neoplasms - secondary ; Lymphatic Metastasis ; Metastasis ; Mice ; Mice, Nude ; Neoplasm Recurrence, Local - metabolism ; Neoplasm Recurrence, Local - prevention & control ; Neoplasm Recurrence, Local - secondary ; Nerve Growth Factors - genetics ; Nerve Growth Factors - metabolism ; Netrin-4 ; Netrins ; Rodents ; Tumor Cells, Cultured ; Tumors ; Vascular endothelial growth factor</subject><ispartof>Oncology reports, 2013-01, Vol.29 (1), p.73-78</ispartof><rights>Copyright © 2013, Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2013</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23124703$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>EVENO, CLARISSE</creatorcontrib><creatorcontrib>CONTRERES, JEAN-OLIVIER</creatorcontrib><creatorcontrib>HAINAUD, PATRICIA</creatorcontrib><creatorcontrib>NEMETH, JUDITH</creatorcontrib><creatorcontrib>DUPUY, EVELYNE</creatorcontrib><creatorcontrib>POCARD, MARC</creatorcontrib><title>Netrin-4 overexpression suppresses primary and metastatic colorectal tumor progression</title><title>Oncology reports</title><addtitle>Oncol Rep</addtitle><description>Tumor angiogenesis is closely associated with clinical staging and has been proposed to correlate with clinical response in terms of subsequent metastases following primary resection. Netrin-4 (NT-4) regulates angiogenic responses. Therefore, we sought to examine the effects of NT-4 on the primary tumor growth of colon cancer cells, liver and lung metastases of colon cancer cells, and responses following primary tumor resection. We used 3 different mouse models of orthotopic primary tumor and liver and lung metastases, comparing 2 human colon cancer cells lines: wild-type (low expression of NT-4) and NT-4 (overexpression of NT-4) LS174 cells. NT-4 overexpression inhibited the primary tumor growth of colorectal LS174 xenografts in nude mice (144.3±12.9 vs. 62.4±4.5 mm3; P<0.0001) as well as its related local and systemic recurrence (38 vs. 0%; P<0.01). NT-4 overexpression also markedly decreased colorectal cancer progression in terms of tumor number and volume of liver metastases in the NT-4 group of the orthotopic liver metastasis model (25 vs. 90% and 4±1 vs. 709±190 mm3, P<0.001 and P<0.05). Collectively, our findings indicate that NT-4 overexpression decreases colorectal lung metastasis and its associated lymph node involvement. NT-4 overexpression decreases tumor recurrence and metastasis after surgical resection, likely via an anti-angiogenic effect. These observations suggest that NT-4 may hold therapeutic potential in the treatment of colorectal cancer growth and major metastatic sites.</description><subject>Angiogenesis</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Cancer therapies</subject><subject>Cell growth</subject><subject>colon cancer</subject><subject>Colonic Neoplasms - metabolism</subject><subject>Colonic Neoplasms - pathology</subject><subject>Colonic Neoplasms - prevention & control</subject><subject>Colorectal cancer</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Humans</subject><subject>Laboratory animals</subject><subject>liver metastasis</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - prevention & control</subject><subject>Liver Neoplasms - secondary</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - prevention & control</subject><subject>Lung Neoplasms - secondary</subject><subject>Lymphatic Metastasis</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Neoplasm Recurrence, Local - metabolism</subject><subject>Neoplasm Recurrence, Local - prevention & control</subject><subject>Neoplasm Recurrence, Local - secondary</subject><subject>Nerve Growth Factors - genetics</subject><subject>Nerve Growth Factors - metabolism</subject><subject>Netrin-4</subject><subject>Netrins</subject><subject>Rodents</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><subject>Vascular endothelial growth factor</subject><issn>1021-335X</issn><issn>1791-2431</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpd0EtLxDAQAOAgiruu3jxLQRAvWTMzTR9HWXzBohcVb6VtEunSNjVpRf-91a0ePM0cvnkydgxiSUmKF9YtUQAuEUS4w-YQp8AxJNgdc4HAieTLjB14vxECYxGl-2yGBBjGgubs-V73rmp5GNh37fRH57T3lW0DP3Q_ufZB56omd59B3qqg0X3u-7yvyqC0tXW67PM66IfGutHZ16n8kO2ZvPb6aIoL9nR99bi65euHm7vV5Zp3KETPqYgxkkYZkqYEjTEqShOlIyMK1GiMjPS4qlRoVAKRpFhAgUkuYyCjgGjBzrd9x9lvg_Z91lS-1HWdt9oOPgOQIChKUznS0390YwfXjttlkBJGUYLhtzqZ1FA0WmXT7dnvx0ZwtgW-G_9RKev_jHUcUy6ACxETfQFE4Xn4</recordid><startdate>201301</startdate><enddate>201301</enddate><creator>EVENO, CLARISSE</creator><creator>CONTRERES, JEAN-OLIVIER</creator><creator>HAINAUD, PATRICIA</creator><creator>NEMETH, JUDITH</creator><creator>DUPUY, EVELYNE</creator><creator>POCARD, MARC</creator><general>D.A. Spandidos</general><general>Spandidos Publications UK Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>201301</creationdate><title>Netrin-4 overexpression suppresses primary and metastatic colorectal tumor progression</title><author>EVENO, CLARISSE ; CONTRERES, JEAN-OLIVIER ; HAINAUD, PATRICIA ; NEMETH, JUDITH ; DUPUY, EVELYNE ; POCARD, MARC</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p200t-3b7265fdf35fc1e272d398de6f0b2e2ff56e3125d2fd81653701b28a5713fd133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Angiogenesis</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Cancer therapies</topic><topic>Cell growth</topic><topic>colon cancer</topic><topic>Colonic Neoplasms - metabolism</topic><topic>Colonic Neoplasms - pathology</topic><topic>Colonic Neoplasms - prevention & control</topic><topic>Colorectal cancer</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Humans</topic><topic>Laboratory animals</topic><topic>liver metastasis</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - prevention & control</topic><topic>Liver Neoplasms - secondary</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - prevention & control</topic><topic>Lung Neoplasms - secondary</topic><topic>Lymphatic Metastasis</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Neoplasm Recurrence, Local - metabolism</topic><topic>Neoplasm Recurrence, Local - prevention & control</topic><topic>Neoplasm Recurrence, Local - secondary</topic><topic>Nerve Growth Factors - genetics</topic><topic>Nerve Growth Factors - metabolism</topic><topic>Netrin-4</topic><topic>Netrins</topic><topic>Rodents</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><topic>Vascular endothelial growth factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>EVENO, CLARISSE</creatorcontrib><creatorcontrib>CONTRERES, JEAN-OLIVIER</creatorcontrib><creatorcontrib>HAINAUD, PATRICIA</creatorcontrib><creatorcontrib>NEMETH, JUDITH</creatorcontrib><creatorcontrib>DUPUY, EVELYNE</creatorcontrib><creatorcontrib>POCARD, MARC</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest - 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Academic</collection><jtitle>Oncology reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>EVENO, CLARISSE</au><au>CONTRERES, JEAN-OLIVIER</au><au>HAINAUD, PATRICIA</au><au>NEMETH, JUDITH</au><au>DUPUY, EVELYNE</au><au>POCARD, MARC</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Netrin-4 overexpression suppresses primary and metastatic colorectal tumor progression</atitle><jtitle>Oncology reports</jtitle><addtitle>Oncol Rep</addtitle><date>2013-01</date><risdate>2013</risdate><volume>29</volume><issue>1</issue><spage>73</spage><epage>78</epage><pages>73-78</pages><issn>1021-335X</issn><eissn>1791-2431</eissn><abstract>Tumor angiogenesis is closely associated with clinical staging and has been proposed to correlate with clinical response in terms of subsequent metastases following primary resection. Netrin-4 (NT-4) regulates angiogenic responses. Therefore, we sought to examine the effects of NT-4 on the primary tumor growth of colon cancer cells, liver and lung metastases of colon cancer cells, and responses following primary tumor resection. We used 3 different mouse models of orthotopic primary tumor and liver and lung metastases, comparing 2 human colon cancer cells lines: wild-type (low expression of NT-4) and NT-4 (overexpression of NT-4) LS174 cells. NT-4 overexpression inhibited the primary tumor growth of colorectal LS174 xenografts in nude mice (144.3±12.9 vs. 62.4±4.5 mm3; P<0.0001) as well as its related local and systemic recurrence (38 vs. 0%; P<0.01). NT-4 overexpression also markedly decreased colorectal cancer progression in terms of tumor number and volume of liver metastases in the NT-4 group of the orthotopic liver metastasis model (25 vs. 90% and 4±1 vs. 709±190 mm3, P<0.001 and P<0.05). Collectively, our findings indicate that NT-4 overexpression decreases colorectal lung metastasis and its associated lymph node involvement. NT-4 overexpression decreases tumor recurrence and metastasis after surgical resection, likely via an anti-angiogenic effect. These observations suggest that NT-4 may hold therapeutic potential in the treatment of colorectal cancer growth and major metastatic sites.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>23124703</pmid><doi>10.3892/or.2012.2104</doi><tpages>6</tpages></addata></record> |
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| ispartof | Oncology reports, 2013-01, Vol.29 (1), p.73-78 |
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| subjects | Angiogenesis Animals Apoptosis Cancer therapies Cell growth colon cancer Colonic Neoplasms - metabolism Colonic Neoplasms - pathology Colonic Neoplasms - prevention & control Colorectal cancer Disease Progression Female Humans Laboratory animals liver metastasis Liver Neoplasms - metabolism Liver Neoplasms - prevention & control Liver Neoplasms - secondary Lung Neoplasms - metabolism Lung Neoplasms - prevention & control Lung Neoplasms - secondary Lymphatic Metastasis Metastasis Mice Mice, Nude Neoplasm Recurrence, Local - metabolism Neoplasm Recurrence, Local - prevention & control Neoplasm Recurrence, Local - secondary Nerve Growth Factors - genetics Nerve Growth Factors - metabolism Netrin-4 Netrins Rodents Tumor Cells, Cultured Tumors Vascular endothelial growth factor |
| title | Netrin-4 overexpression suppresses primary and metastatic colorectal tumor progression |
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