Integrin β1, Osmosensing, and Chemoresistance in Mouse Ehrlich Carcinoma Cells
Background/Aims: Altered expression of the integrin family of cell adhesion receptors has been associated with initiation, progression, and metastasis of solid tumors as well as in the development of chemoresistance. Here, we investigated the role of integrins, in particular integrin β1, in cell vol...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2015-04-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/374057 |
| _version_ | 1819108736671678464 |
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| author | Belinda Halling Sørensen Line Jee Hartmann Rasmussen Bjørn Sindballe Broberg Thomas Kjær Klausen Daniel Peter Rafael Sauter Ian Henry Lambert Anders Aspberg Else Kay Hoffmann |
| author_facet | Belinda Halling Sørensen Line Jee Hartmann Rasmussen Bjørn Sindballe Broberg Thomas Kjær Klausen Daniel Peter Rafael Sauter Ian Henry Lambert Anders Aspberg Else Kay Hoffmann |
| author_sort | Belinda Halling Sørensen |
| collection | DOAJ |
| description | Background/Aims: Altered expression of the integrin family of cell adhesion receptors has been associated with initiation, progression, and metastasis of solid tumors as well as in the development of chemoresistance. Here, we investigated the role of integrins, in particular integrin β1, in cell volume regulation and drug-induced apoptosis in adherent and non-adherent Ehrlich ascites cell lines. Methods: Adhesion phenotypes were verified by colorimetric cell-adhesion-assay. Quantitative real-time PCR and western blot were used to compare expression levels of integrin subunits. Small interfering RNA was used to silence integrin β1 expression. Regulatory volume decrease (RVD) after cell swelling was studied with calcein-fluorescence-self-quenching and Coulter counter analysis. Taurine efflux was estimated with tracer technique. Caspase assay was used to determine apoptosis. Results: We show that adherent cells have stronger fibronectin binding and a significantly increased expression of integrin α5, αv, and β1 at mRNA and protein level, compared to non-adherent cells. Knockdown of integrin β1 reduced RVD of the adherent but not of the non-adherent cells. Efflux of taurine was unaffected. In contrast to non-adherent, adherent cells exhibited chemoresistance to chemotherapeutic drugs (cisplatin and gemcitabine). However, knockdown of integrin β1 promoted cisplatin-induced caspase activity in adherent cells. Conclusion: Our data identifies integrin β1 as a part of the osmosensing machinery and regulator of cisplatin resistance in adherent Ehrlich cells. |
| first_indexed | 2024-12-22T03:14:40Z |
| format | Article |
| id | doaj.art-8329f77e72384517abf9756bd934a2b5 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-22T03:14:40Z |
| publishDate | 2015-04-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-8329f77e72384517abf9756bd934a2b52022-12-21T18:40:51ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-04-0136111113210.1159/000374057374057Integrin β1, Osmosensing, and Chemoresistance in Mouse Ehrlich Carcinoma CellsBelinda Halling SørensenLine Jee Hartmann RasmussenBjørn Sindballe BrobergThomas Kjær KlausenDaniel Peter Rafael SauterIan Henry LambertAnders AspbergElse Kay HoffmannBackground/Aims: Altered expression of the integrin family of cell adhesion receptors has been associated with initiation, progression, and metastasis of solid tumors as well as in the development of chemoresistance. Here, we investigated the role of integrins, in particular integrin β1, in cell volume regulation and drug-induced apoptosis in adherent and non-adherent Ehrlich ascites cell lines. Methods: Adhesion phenotypes were verified by colorimetric cell-adhesion-assay. Quantitative real-time PCR and western blot were used to compare expression levels of integrin subunits. Small interfering RNA was used to silence integrin β1 expression. Regulatory volume decrease (RVD) after cell swelling was studied with calcein-fluorescence-self-quenching and Coulter counter analysis. Taurine efflux was estimated with tracer technique. Caspase assay was used to determine apoptosis. Results: We show that adherent cells have stronger fibronectin binding and a significantly increased expression of integrin α5, αv, and β1 at mRNA and protein level, compared to non-adherent cells. Knockdown of integrin β1 reduced RVD of the adherent but not of the non-adherent cells. Efflux of taurine was unaffected. In contrast to non-adherent, adherent cells exhibited chemoresistance to chemotherapeutic drugs (cisplatin and gemcitabine). However, knockdown of integrin β1 promoted cisplatin-induced caspase activity in adherent cells. Conclusion: Our data identifies integrin β1 as a part of the osmosensing machinery and regulator of cisplatin resistance in adherent Ehrlich cells.http://www.karger.com/Article/FullText/374057IntegrinCisplatinGemcitabineEhrlich Ascites Tumor CellsMulti-drug-resistanceHypotonic cell swelling |
| spellingShingle | Belinda Halling Sørensen Line Jee Hartmann Rasmussen Bjørn Sindballe Broberg Thomas Kjær Klausen Daniel Peter Rafael Sauter Ian Henry Lambert Anders Aspberg Else Kay Hoffmann Integrin β1, Osmosensing, and Chemoresistance in Mouse Ehrlich Carcinoma Cells Cellular Physiology and Biochemistry Integrin Cisplatin Gemcitabine Ehrlich Ascites Tumor Cells Multi-drug-resistance Hypotonic cell swelling |
| title | Integrin β1, Osmosensing, and Chemoresistance in Mouse Ehrlich Carcinoma Cells |
| title_full | Integrin β1, Osmosensing, and Chemoresistance in Mouse Ehrlich Carcinoma Cells |
| title_fullStr | Integrin β1, Osmosensing, and Chemoresistance in Mouse Ehrlich Carcinoma Cells |
| title_full_unstemmed | Integrin β1, Osmosensing, and Chemoresistance in Mouse Ehrlich Carcinoma Cells |
| title_short | Integrin β1, Osmosensing, and Chemoresistance in Mouse Ehrlich Carcinoma Cells |
| title_sort | integrin β1 osmosensing and chemoresistance in mouse ehrlich carcinoma cells |
| topic | Integrin Cisplatin Gemcitabine Ehrlich Ascites Tumor Cells Multi-drug-resistance Hypotonic cell swelling |
| url | http://www.karger.com/Article/FullText/374057 |
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