Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathway
<p>Abstract</p> <p>Background</p> <p>Melanomas are highly malignant and have high metastatic potential; hence, there is a need for new therapeutic strategies to prevent cell metastasis. In the present study, we investigated whether statins inhibit tumor cell migration,...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-09-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Online Access: | http://www.jeccr.com/content/29/1/127 |
| _version_ | 1818522214157254656 |
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| author | Isozaki Misako Itoh Tatsuki Satou Takao Ogaki Mitsuhiko Nakamura Haruyuki Shoji Kaori Yamazoe Yuzuru Tsubaki Masanobu Kidera Yasuhiro Kaneko Junichi Tanimori Yoshihiro Yanae Masashi Nishida Shozo |
| author_facet | Isozaki Misako Itoh Tatsuki Satou Takao Ogaki Mitsuhiko Nakamura Haruyuki Shoji Kaori Yamazoe Yuzuru Tsubaki Masanobu Kidera Yasuhiro Kaneko Junichi Tanimori Yoshihiro Yanae Masashi Nishida Shozo |
| author_sort | Isozaki Misako |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Melanomas are highly malignant and have high metastatic potential; hence, there is a need for new therapeutic strategies to prevent cell metastasis. In the present study, we investigated whether statins inhibit tumor cell migration, invasion, adhesion, and metastasis in the B16BL6 mouse melanoma cell line.</p> <p>Methods</p> <p>The cytotoxicity of statins toward the B16BL6 cells were evaluated using a cell viability assay. As an experimental model, B16BL6 cells were intravenously injected into C57BL/6 mice. Cell migration and invasion were assessed using Boyden chamber assays. Cell adhesion analysis was performed using type I collagen-, type IV collagen-, fibronectin-, and laminin-coated plates. The mRNA levels, enzyme activities and protein levels of matrix metalloproteinases (MMPs) were determined using RT-PCR, activity assay kits, and Western blot analysis, respectively; the mRNA and protein levels of vary late antigens (VLAs) were also determined. The effects of statins on signal transduction molecules were determined by western blot analyses.</p> <p>Results</p> <p>We found that statins significantly inhibited lung metastasis, cell migration, invasion, and adhesion at concentrations that did not have cytotoxic effects on B16BL6 cells. Statins also inhibited the mRNA expressions and enzymatic activities of matrix metalloproteinases (MMPs). Moreover, they suppressed the mRNA and protein expressions of integrin α<sub>2</sub>, integrin α<sub>4</sub>, and integrin α<sub>5 </sub>and decreased the membrane localization of Rho, and phosphorylated LIM kinase (LIMK) and myosin light chain (MLC).</p> <p>Conclusions</p> <p>The results indicated that statins suppressed the Rho/Rho-associated coiled-coil-containing protein kinase (ROCK) pathways, thereby inhibiting B16BL6 cell migration, invasion, adhesion, and metastasis. Furthermore, they markedly inhibited clinically evident metastasis. Thus, these findings suggest that statins have potential clinical applications for the treatment of tumor cell metastasis.</p> |
| first_indexed | 2024-12-11T05:30:19Z |
| format | Article |
| id | doaj.art-44caf9f5c1c84a6aac8011563202c8f2 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-11T05:30:19Z |
| publishDate | 2010-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-44caf9f5c1c84a6aac8011563202c8f22022-12-22T01:19:27ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662010-09-0129112710.1186/1756-9966-29-127Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathwayIsozaki MisakoItoh TatsukiSatou TakaoOgaki MitsuhikoNakamura HaruyukiShoji KaoriYamazoe YuzuruTsubaki MasanobuKidera YasuhiroKaneko JunichiTanimori YoshihiroYanae MasashiNishida Shozo<p>Abstract</p> <p>Background</p> <p>Melanomas are highly malignant and have high metastatic potential; hence, there is a need for new therapeutic strategies to prevent cell metastasis. In the present study, we investigated whether statins inhibit tumor cell migration, invasion, adhesion, and metastasis in the B16BL6 mouse melanoma cell line.</p> <p>Methods</p> <p>The cytotoxicity of statins toward the B16BL6 cells were evaluated using a cell viability assay. As an experimental model, B16BL6 cells were intravenously injected into C57BL/6 mice. Cell migration and invasion were assessed using Boyden chamber assays. Cell adhesion analysis was performed using type I collagen-, type IV collagen-, fibronectin-, and laminin-coated plates. The mRNA levels, enzyme activities and protein levels of matrix metalloproteinases (MMPs) were determined using RT-PCR, activity assay kits, and Western blot analysis, respectively; the mRNA and protein levels of vary late antigens (VLAs) were also determined. The effects of statins on signal transduction molecules were determined by western blot analyses.</p> <p>Results</p> <p>We found that statins significantly inhibited lung metastasis, cell migration, invasion, and adhesion at concentrations that did not have cytotoxic effects on B16BL6 cells. Statins also inhibited the mRNA expressions and enzymatic activities of matrix metalloproteinases (MMPs). Moreover, they suppressed the mRNA and protein expressions of integrin α<sub>2</sub>, integrin α<sub>4</sub>, and integrin α<sub>5 </sub>and decreased the membrane localization of Rho, and phosphorylated LIM kinase (LIMK) and myosin light chain (MLC).</p> <p>Conclusions</p> <p>The results indicated that statins suppressed the Rho/Rho-associated coiled-coil-containing protein kinase (ROCK) pathways, thereby inhibiting B16BL6 cell migration, invasion, adhesion, and metastasis. Furthermore, they markedly inhibited clinically evident metastasis. Thus, these findings suggest that statins have potential clinical applications for the treatment of tumor cell metastasis.</p>http://www.jeccr.com/content/29/1/127 |
| spellingShingle | Isozaki Misako Itoh Tatsuki Satou Takao Ogaki Mitsuhiko Nakamura Haruyuki Shoji Kaori Yamazoe Yuzuru Tsubaki Masanobu Kidera Yasuhiro Kaneko Junichi Tanimori Yoshihiro Yanae Masashi Nishida Shozo Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathway Journal of Experimental & Clinical Cancer Research |
| title | Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathway |
| title_full | Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathway |
| title_fullStr | Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathway |
| title_full_unstemmed | Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathway |
| title_short | Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathway |
| title_sort | reduction of lung metastasis cell invasion and adhesion in mouse melanoma by statin induced blockade of the rho rho associated coiled coil containing protein kinase pathway |
| url | http://www.jeccr.com/content/29/1/127 |
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