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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Main Authors: Ogawa K., Pitchakarn P., Suzuki S., Chewonarin T., Tang M., Takahashi S., Naiki-Ito A., Sato S., Asamoto M., Shirai T.
Format: Article
Language:English
Published: 2014
Online Access:http://www.scopus.com/inward/record.url?eid=2-s2.0-84860250064&partnerID=40&md5=f9d823e68c5bab62932ec68f79003d35
http://cmuir.cmu.ac.th/handle/6653943832/3831
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spelling th-cmuir.6653943832-38312014-08-30T02:35:22Z Silencing of connexin 43 suppresses invasion, migration and lung metastasis of rat hepatocellular carcinoma cells Ogawa K. Pitchakarn P. Suzuki S. Chewonarin T. Tang M. Takahashi S. Naiki-Ito A. Sato S. Asamoto M. Shirai T. 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. © 2012 Japanese Cancer Association. 2014-08-30T02:35:22Z 2014-08-30T02:35:22Z 2012 Article 13479032 10.1111/j.1349-7006.2012.02228.x 22320152 CSACC http://www.scopus.com/inward/record.url?eid=2-s2.0-84860250064&partnerID=40&md5=f9d823e68c5bab62932ec68f79003d35 http://cmuir.cmu.ac.th/handle/6653943832/3831 English
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
language English
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. © 2012 Japanese Cancer Association.
format Article
author Ogawa K.
Pitchakarn P.
Suzuki S.
Chewonarin T.
Tang M.
Takahashi S.
Naiki-Ito A.
Sato S.
Asamoto M.
Shirai T.
spellingShingle Ogawa K.
Pitchakarn P.
Suzuki S.
Chewonarin T.
Tang M.
Takahashi S.
Naiki-Ito A.
Sato S.
Asamoto M.
Shirai T.
Silencing of connexin 43 suppresses invasion, migration and lung metastasis of rat hepatocellular carcinoma cells
author_facet Ogawa K.
Pitchakarn P.
Suzuki S.
Chewonarin T.
Tang M.
Takahashi S.
Naiki-Ito A.
Sato S.
Asamoto M.
Shirai T.
author_sort Ogawa K.
title Silencing of connexin 43 suppresses invasion, migration and lung metastasis of rat hepatocellular carcinoma cells
title_short Silencing of connexin 43 suppresses invasion, migration and lung metastasis of rat hepatocellular carcinoma cells
title_full Silencing of connexin 43 suppresses invasion, migration and lung metastasis of rat hepatocellular carcinoma cells
title_fullStr Silencing of connexin 43 suppresses invasion, migration and lung metastasis of rat hepatocellular carcinoma cells
title_full_unstemmed Silencing of connexin 43 suppresses invasion, migration and lung metastasis of rat hepatocellular carcinoma cells
title_sort silencing of connexin 43 suppresses invasion, migration and lung metastasis of rat hepatocellular carcinoma cells
publishDate 2014
url http://www.scopus.com/inward/record.url?eid=2-s2.0-84860250064&partnerID=40&md5=f9d823e68c5bab62932ec68f79003d35
http://cmuir.cmu.ac.th/handle/6653943832/3831
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