Silencing of connexin 43 suppresses invasion, migration and lung metastasis of rat hepatocellular carcinoma cells
To reduce cancer mortality, understanding of mechanisms of cancer metastasis is crucial. We have established six rat hepatocellular carcinoma (HCC) cell lines, which exhibit differing metastatic potential to the lung after inoculation into the tail veins of nude mice. In the present experiment, we i...
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| Veröffentlicht in: | Cancer science 2012-05, Vol.103 (5), p.860-867 |
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| creator | Ogawa, Kumiko Pitchakarn, Pornsiri Suzuki, Shugo Chewonarin, Teera Tang, MingXi Takahashi, Seishiro Naiki‐Ito, Aya Sato, Shinya Takahashi, Satoru Asamoto, Makoto Shirai, Tomoyuki |
| description | To reduce cancer mortality, understanding of mechanisms of cancer metastasis is crucial. We have established six rat hepatocellular carcinoma (HCC) cell lines, which exhibit differing metastatic potential to the lung after inoculation into the tail veins of nude mice. In the present experiment, we investigated the process of cell attachment to metastatic sites and possible regulating factors. One hour after inoculation, two of two HCC cell lines with high metastatic potential and one of two HCC cell lines with low metastatic potential exhibited many attached cells in the lung. One day after inoculation, lung metastatic foci were observed only with highly‐metastatic cells with elevated connexin 43 (Cx43) expression as assessed by cDNA array analysis. Furthermore, 24 or 48 h after transfection of an siRNA targeting Cx43, in vitro invasion and migration were suppressed by 68% (P |
| doi_str_mv | 10.1111/j.1349-7006.2012.02228.x |
| format | Article |
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We have established six rat hepatocellular carcinoma (HCC) cell lines, which exhibit differing metastatic potential to the lung after inoculation into the tail veins of nude mice. In the present experiment, we investigated the process of cell attachment to metastatic sites and possible regulating factors. One hour after inoculation, two of two HCC cell lines with high metastatic potential and one of two HCC cell lines with low metastatic potential exhibited many attached cells in the lung. One day after inoculation, lung metastatic foci were observed only with highly‐metastatic cells with elevated connexin 43 (Cx43) expression as assessed by cDNA array analysis. Furthermore, 24 or 48 h after transfection of an siRNA targeting Cx43, in vitro invasion and migration were suppressed by 68% (P < 0.001) and 36% (P < 0.05) compared with control‐siRNA transfected cells, despite no differences in cellular morphology, cell proliferation or apoptotic activity. Moreover, the number of metastatic nodules per lung area in nude mice was significantly (P < 0.01) reduced. In conclusion, suppression of Cx43 expression in tumor cells reduced in vitro migration and invasion capacity and in vivo metastatic ability so that Cx43 has potential as a molecular target for prevention of cancer metastasis with Cx43 overexpressing tumors. (Cancer Sci 2012; 103: 860–867)</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/j.1349-7006.2012.02228.x</identifier><identifier>PMID: 22320152</identifier><language>eng</language><publisher>England: John Wiley and Sons Inc</publisher><subject>Animals ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - secondary ; Cell Line, Tumor ; Cell Movement - genetics ; Connexin 43 - genetics ; Gene Silencing ; Liver Neoplasms - genetics ; Liver Neoplasms - pathology ; Lung Neoplasms - genetics ; Lung Neoplasms - secondary ; Mice ; Mice, Nude ; Neoplasm Invasiveness ; Neoplasm Transplantation ; Original ; Rats</subject><ispartof>Cancer science, 2012-05, Vol.103 (5), p.860-867</ispartof><rights>2012 Japanese Cancer Association</rights><rights>2012 Japanese Cancer Association.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5648-ca190f68fa809cc2bc6a19770b77ed0f618a3cf1357bbab627306957d41f963f3</citedby><cites>FETCH-LOGICAL-c5648-ca190f68fa809cc2bc6a19770b77ed0f618a3cf1357bbab627306957d41f963f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659240/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659240/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><linktorsrc>$$Uhttps://onlinelibrary.wiley.com/doi/abs/10.1111%2Fj.1349-7006.2012.02228.x$$EView_record_in_Wiley-Blackwell$$FView_record_in_$$GWiley-Blackwell</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22320152$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ogawa, Kumiko</creatorcontrib><creatorcontrib>Pitchakarn, Pornsiri</creatorcontrib><creatorcontrib>Suzuki, Shugo</creatorcontrib><creatorcontrib>Chewonarin, Teera</creatorcontrib><creatorcontrib>Tang, MingXi</creatorcontrib><creatorcontrib>Takahashi, Seishiro</creatorcontrib><creatorcontrib>Naiki‐Ito, Aya</creatorcontrib><creatorcontrib>Sato, Shinya</creatorcontrib><creatorcontrib>Takahashi, Satoru</creatorcontrib><creatorcontrib>Asamoto, Makoto</creatorcontrib><creatorcontrib>Shirai, Tomoyuki</creatorcontrib><title>Silencing of connexin 43 suppresses invasion, migration and lung metastasis of rat hepatocellular carcinoma cells</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>To reduce cancer mortality, understanding of mechanisms of cancer metastasis is crucial. We have established six rat hepatocellular carcinoma (HCC) cell lines, which exhibit differing metastatic potential to the lung after inoculation into the tail veins of nude mice. In the present experiment, we investigated the process of cell attachment to metastatic sites and possible regulating factors. One hour after inoculation, two of two HCC cell lines with high metastatic potential and one of two HCC cell lines with low metastatic potential exhibited many attached cells in the lung. One day after inoculation, lung metastatic foci were observed only with highly‐metastatic cells with elevated connexin 43 (Cx43) expression as assessed by cDNA array analysis. Furthermore, 24 or 48 h after transfection of an siRNA targeting Cx43, in vitro invasion and migration were suppressed by 68% (P < 0.001) and 36% (P < 0.05) compared with control‐siRNA transfected cells, despite no differences in cellular morphology, cell proliferation or apoptotic activity. Moreover, the number of metastatic nodules per lung area in nude mice was significantly (P < 0.01) reduced. In conclusion, suppression of Cx43 expression in tumor cells reduced in vitro migration and invasion capacity and in vivo metastatic ability so that Cx43 has potential as a molecular target for prevention of cancer metastasis with Cx43 overexpressing tumors. (Cancer Sci 2012; 103: 860–867)</description><subject>Animals</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - secondary</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - genetics</subject><subject>Connexin 43 - genetics</subject><subject>Gene Silencing</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - pathology</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - secondary</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Transplantation</subject><subject>Original</subject><subject>Rats</subject><issn>1347-9032</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUctO3DAUtaqiQml_ofKSRZP6kdjxokhoRB8SEgtgbd14nMGjxA52AsPf4zB01O5qWfLRPQ_bOghhSkqa17dtSXmlCkmIKBmhrCSMsabcvUMnB-L9K5aFIpwdo48pbQnholLVB3TMGM-2mp2ghxvXW2-c3-DQYRO8tzvnccVxmscx2pRsws4_QnLBf8WD20SYMsTg17ifs22wE6S8XVoSMovv7QhTMLbv5x4iNhBzfhgAL6P0CR110Cf7-e08RXc_Lm9Xv4qr65-_VxdXhalF1RQGqCKdaDpoiDKGtUbkiZSkldKuM0Mb4KajvJZtC61gkhOharmuaKcE7_gpOt_njnM72LWxforQ6zG6AeKzDuD0v4x393oTHrUUtWIVyQFnbwExPMw2TXpwafkCeBvmpCkhqqGsEk2WNnupiSGlaLvDNZTopTG91UsxeilGL43p18b0Llu__P3Mg_FPRVnwfS94yk09_3ewXl3cLIi_AMapp3A</recordid><startdate>201205</startdate><enddate>201205</enddate><creator>Ogawa, Kumiko</creator><creator>Pitchakarn, Pornsiri</creator><creator>Suzuki, Shugo</creator><creator>Chewonarin, Teera</creator><creator>Tang, MingXi</creator><creator>Takahashi, Seishiro</creator><creator>Naiki‐Ito, Aya</creator><creator>Sato, Shinya</creator><creator>Takahashi, Satoru</creator><creator>Asamoto, Makoto</creator><creator>Shirai, Tomoyuki</creator><general>John Wiley and Sons Inc</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><scope>5PM</scope></search><sort><creationdate>201205</creationdate><title>Silencing of connexin 43 suppresses invasion, migration and lung metastasis of rat hepatocellular carcinoma cells</title><author>Ogawa, Kumiko ; Pitchakarn, Pornsiri ; Suzuki, Shugo ; Chewonarin, Teera ; Tang, MingXi ; Takahashi, Seishiro ; Naiki‐Ito, Aya ; Sato, Shinya ; Takahashi, Satoru ; Asamoto, Makoto ; Shirai, Tomoyuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5648-ca190f68fa809cc2bc6a19770b77ed0f618a3cf1357bbab627306957d41f963f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - secondary</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - genetics</topic><topic>Connexin 43 - genetics</topic><topic>Gene Silencing</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - pathology</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - secondary</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplasm Transplantation</topic><topic>Original</topic><topic>Rats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ogawa, Kumiko</creatorcontrib><creatorcontrib>Pitchakarn, Pornsiri</creatorcontrib><creatorcontrib>Suzuki, Shugo</creatorcontrib><creatorcontrib>Chewonarin, Teera</creatorcontrib><creatorcontrib>Tang, MingXi</creatorcontrib><creatorcontrib>Takahashi, Seishiro</creatorcontrib><creatorcontrib>Naiki‐Ito, Aya</creatorcontrib><creatorcontrib>Sato, Shinya</creatorcontrib><creatorcontrib>Takahashi, Satoru</creatorcontrib><creatorcontrib>Asamoto, Makoto</creatorcontrib><creatorcontrib>Shirai, Tomoyuki</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Ogawa, Kumiko</au><au>Pitchakarn, Pornsiri</au><au>Suzuki, Shugo</au><au>Chewonarin, Teera</au><au>Tang, MingXi</au><au>Takahashi, Seishiro</au><au>Naiki‐Ito, Aya</au><au>Sato, Shinya</au><au>Takahashi, Satoru</au><au>Asamoto, Makoto</au><au>Shirai, Tomoyuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Silencing of connexin 43 suppresses invasion, migration and lung metastasis of rat hepatocellular carcinoma cells</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2012-05</date><risdate>2012</risdate><volume>103</volume><issue>5</issue><spage>860</spage><epage>867</epage><pages>860-867</pages><issn>1347-9032</issn><eissn>1349-7006</eissn><abstract>To reduce cancer mortality, understanding of mechanisms of cancer metastasis is crucial. We have established six rat hepatocellular carcinoma (HCC) cell lines, which exhibit differing metastatic potential to the lung after inoculation into the tail veins of nude mice. In the present experiment, we investigated the process of cell attachment to metastatic sites and possible regulating factors. One hour after inoculation, two of two HCC cell lines with high metastatic potential and one of two HCC cell lines with low metastatic potential exhibited many attached cells in the lung. One day after inoculation, lung metastatic foci were observed only with highly‐metastatic cells with elevated connexin 43 (Cx43) expression as assessed by cDNA array analysis. Furthermore, 24 or 48 h after transfection of an siRNA targeting Cx43, in vitro invasion and migration were suppressed by 68% (P < 0.001) and 36% (P < 0.05) compared with control‐siRNA transfected cells, despite no differences in cellular morphology, cell proliferation or apoptotic activity. Moreover, the number of metastatic nodules per lung area in nude mice was significantly (P < 0.01) reduced. In conclusion, suppression of Cx43 expression in tumor cells reduced in vitro migration and invasion capacity and in vivo metastatic ability so that Cx43 has potential as a molecular target for prevention of cancer metastasis with Cx43 overexpressing tumors. (Cancer Sci 2012; 103: 860–867)</abstract><cop>England</cop><pub>John Wiley and Sons Inc</pub><pmid>22320152</pmid><doi>10.1111/j.1349-7006.2012.02228.x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - secondary Cell Line, Tumor Cell Movement - genetics Connexin 43 - genetics Gene Silencing Liver Neoplasms - genetics Liver Neoplasms - pathology Lung Neoplasms - genetics Lung Neoplasms - secondary Mice Mice, Nude Neoplasm Invasiveness Neoplasm Transplantation Original Rats |
| title | Silencing of connexin 43 suppresses invasion, migration and lung metastasis of rat hepatocellular carcinoma cells |
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