MicroRNA-128 Confers Anti-Endothelial Adhesion and Anti-Migration Properties to Counteract Highly Metastatic Cervical Cancer Cells’ Migration in a Parallel-Plate Flow Chamber
Despite the distant metastasis of cervical cancer cells being a prominent cause of mortality, neither the metastasis capacity nor the in vitro conditions mimicking adhesion of cervical cancer cells to endothelial cells have been fully elucidated. Circulating metastatic cancer cells undergo transendo...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-12-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/1/215 |
| _version_ | 1797543315306971136 |
|---|---|
| author | Pei-Chin Chuang Chun-Wun Lu Ching-Chin Tsai Shun-Hung Tseng Wen-Hong Su |
| author_facet | Pei-Chin Chuang Chun-Wun Lu Ching-Chin Tsai Shun-Hung Tseng Wen-Hong Su |
| author_sort | Pei-Chin Chuang |
| collection | DOAJ |
| description | Despite the distant metastasis of cervical cancer cells being a prominent cause of mortality, neither the metastasis capacity nor the in vitro conditions mimicking adhesion of cervical cancer cells to endothelial cells have been fully elucidated. Circulating metastatic cancer cells undergo transendothelial migration and invade normal organs in distant metastasis; however, the putative molecular mechanism remains largely uncertain. In this study, we describe the use of an in vitro parallel-plate flow chamber to simulate the dynamic circulation stress on cervical cancer cells and elucidate their vascular adhesion and metastasis. We isolate the viable and shear stress-resistant (SSR) cervical cancer cells for mechanistic studies. Remarkably, the identified SSR-HeLa and SSR-CaSki exhibited high in vitro adhesive and metastatic activities. Hence, a consistently suppressed <i>miR-128</i> level was revealed in SSR cell clones compared to those of parental wild-type (WT) cells. Overexpressed <i>miR-128</i> attenuated SSR-HeLa cells’ adherence to human umbilical cord vein endothelial cells (HUVECs); in contrast, suppressed <i>miR-128</i> efficiently augmented the static adhesion capacity in WT-HeLa and WT-CaSki cells. Hence, amplified <i>miR-128</i> modestly abolished in vitro SSR-augmented HeLa and CaSki cell movement, whereas reduced <i>miR-128</i> aggravated the migration speed in a time-lapse recording assay in WT groups. Consistently, the force expression of <i>miR-128</i> alleviated the SSR-enhanced HeLa and CaSki cell mobility in a wound healing assay. Notably, miR-128 mediated SSR-enhanced HeLa and CaSki cells’ adhesion and metastasis through suppressed <i>ITGA5</i>, <i>ITGB5</i>, <i>sLex</i>, <i>CEACAM-6</i>, <i>MMP9</i>, and <i>MMP23</i> transcript levels. Our data provide evidence suggesting that <i>miR-128</i> is a promising microRNA that prevented endothelial cells’ adhesion and transendothelial migration to contribute to the SSR-enhanced adhesion and metastasis progression under a parallel-plate flow chamber system. This indicates that the nucleoid-based <i>miR-128</i> strategy may be an attractive therapeutic strategy to eliminate tumor cells resistant to circulation shear flow, prevent vascular adhesion, and preclude subsequent transendothelial metastasis. |
| first_indexed | 2024-03-10T13:43:45Z |
| format | Article |
| id | doaj.art-a4f61f38655440c4b193f0f3c3430796 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:43:45Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a4f61f38655440c4b193f0f3c34307962023-11-21T02:50:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-0122121510.3390/ijms22010215MicroRNA-128 Confers Anti-Endothelial Adhesion and Anti-Migration Properties to Counteract Highly Metastatic Cervical Cancer Cells’ Migration in a Parallel-Plate Flow ChamberPei-Chin Chuang0Chun-Wun Lu1Ching-Chin Tsai2Shun-Hung Tseng3Wen-Hong Su4Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDespite the distant metastasis of cervical cancer cells being a prominent cause of mortality, neither the metastasis capacity nor the in vitro conditions mimicking adhesion of cervical cancer cells to endothelial cells have been fully elucidated. Circulating metastatic cancer cells undergo transendothelial migration and invade normal organs in distant metastasis; however, the putative molecular mechanism remains largely uncertain. In this study, we describe the use of an in vitro parallel-plate flow chamber to simulate the dynamic circulation stress on cervical cancer cells and elucidate their vascular adhesion and metastasis. We isolate the viable and shear stress-resistant (SSR) cervical cancer cells for mechanistic studies. Remarkably, the identified SSR-HeLa and SSR-CaSki exhibited high in vitro adhesive and metastatic activities. Hence, a consistently suppressed <i>miR-128</i> level was revealed in SSR cell clones compared to those of parental wild-type (WT) cells. Overexpressed <i>miR-128</i> attenuated SSR-HeLa cells’ adherence to human umbilical cord vein endothelial cells (HUVECs); in contrast, suppressed <i>miR-128</i> efficiently augmented the static adhesion capacity in WT-HeLa and WT-CaSki cells. Hence, amplified <i>miR-128</i> modestly abolished in vitro SSR-augmented HeLa and CaSki cell movement, whereas reduced <i>miR-128</i> aggravated the migration speed in a time-lapse recording assay in WT groups. Consistently, the force expression of <i>miR-128</i> alleviated the SSR-enhanced HeLa and CaSki cell mobility in a wound healing assay. Notably, miR-128 mediated SSR-enhanced HeLa and CaSki cells’ adhesion and metastasis through suppressed <i>ITGA5</i>, <i>ITGB5</i>, <i>sLex</i>, <i>CEACAM-6</i>, <i>MMP9</i>, and <i>MMP23</i> transcript levels. Our data provide evidence suggesting that <i>miR-128</i> is a promising microRNA that prevented endothelial cells’ adhesion and transendothelial migration to contribute to the SSR-enhanced adhesion and metastasis progression under a parallel-plate flow chamber system. This indicates that the nucleoid-based <i>miR-128</i> strategy may be an attractive therapeutic strategy to eliminate tumor cells resistant to circulation shear flow, prevent vascular adhesion, and preclude subsequent transendothelial metastasis.https://www.mdpi.com/1422-0067/22/1/215<i>microRNA-128</i>cervical cancer cellscell adhesioncell migrationparallel-plate flow chamber |
| spellingShingle | Pei-Chin Chuang Chun-Wun Lu Ching-Chin Tsai Shun-Hung Tseng Wen-Hong Su MicroRNA-128 Confers Anti-Endothelial Adhesion and Anti-Migration Properties to Counteract Highly Metastatic Cervical Cancer Cells’ Migration in a Parallel-Plate Flow Chamber International Journal of Molecular Sciences <i>microRNA-128</i> cervical cancer cells cell adhesion cell migration parallel-plate flow chamber |
| title | MicroRNA-128 Confers Anti-Endothelial Adhesion and Anti-Migration Properties to Counteract Highly Metastatic Cervical Cancer Cells’ Migration in a Parallel-Plate Flow Chamber |
| title_full | MicroRNA-128 Confers Anti-Endothelial Adhesion and Anti-Migration Properties to Counteract Highly Metastatic Cervical Cancer Cells’ Migration in a Parallel-Plate Flow Chamber |
| title_fullStr | MicroRNA-128 Confers Anti-Endothelial Adhesion and Anti-Migration Properties to Counteract Highly Metastatic Cervical Cancer Cells’ Migration in a Parallel-Plate Flow Chamber |
| title_full_unstemmed | MicroRNA-128 Confers Anti-Endothelial Adhesion and Anti-Migration Properties to Counteract Highly Metastatic Cervical Cancer Cells’ Migration in a Parallel-Plate Flow Chamber |
| title_short | MicroRNA-128 Confers Anti-Endothelial Adhesion and Anti-Migration Properties to Counteract Highly Metastatic Cervical Cancer Cells’ Migration in a Parallel-Plate Flow Chamber |
| title_sort | microrna 128 confers anti endothelial adhesion and anti migration properties to counteract highly metastatic cervical cancer cells migration in a parallel plate flow chamber |
| topic | <i>microRNA-128</i> cervical cancer cells cell adhesion cell migration parallel-plate flow chamber |
| url | https://www.mdpi.com/1422-0067/22/1/215 |
| work_keys_str_mv | AT peichinchuang microrna128confersantiendothelialadhesionandantimigrationpropertiestocounteracthighlymetastaticcervicalcancercellsmigrationinaparallelplateflowchamber AT chunwunlu microrna128confersantiendothelialadhesionandantimigrationpropertiestocounteracthighlymetastaticcervicalcancercellsmigrationinaparallelplateflowchamber AT chingchintsai microrna128confersantiendothelialadhesionandantimigrationpropertiestocounteracthighlymetastaticcervicalcancercellsmigrationinaparallelplateflowchamber AT shunhungtseng microrna128confersantiendothelialadhesionandantimigrationpropertiestocounteracthighlymetastaticcervicalcancercellsmigrationinaparallelplateflowchamber AT wenhongsu microrna128confersantiendothelialadhesionandantimigrationpropertiestocounteracthighlymetastaticcervicalcancercellsmigrationinaparallelplateflowchamber |