Constitutive activation of BMP signalling abrogates experimental metastasis of OVCA429 cells via reduced cell adhesion
Background Activation of bone morphogenetic protein (BMP)4 signalling in human ovarian cancer cells induces a number of phenotypic changes in vitro, including altered cell morphology, adhesion, motility and invasion, relative to normal human ovarian surface epithelial cells. From these in vitro anal...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Shepherd, Trevor G [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2010 |
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| Anmerkung: |
© Shepherd et al; licensee BioMed Central Ltd. 2010 |
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| Übergeordnetes Werk: |
Enthalten in: Journal of ovarian research - London : BioMed Central, 2008, 3(2010), 1 vom: 26. Feb. |
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| Übergeordnetes Werk: |
volume:3 ; year:2010 ; number:1 ; day:26 ; month:02 |
| Links: |
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| DOI / URN: |
10.1186/1757-2215-3-5 |
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| Katalog-ID: |
SPR029664373 |
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| 520 | |a Background Activation of bone morphogenetic protein (BMP)4 signalling in human ovarian cancer cells induces a number of phenotypic changes in vitro, including altered cell morphology, adhesion, motility and invasion, relative to normal human ovarian surface epithelial cells. From these in vitro analyses, we had hypothesized that active BMP signalling promotes the metastatic potential of ovarian cancer. Methods To test this directly, we engineered OVCA429 human ovarian cancer cells possessing doxycycline-inducible expression of a constitutively-active mutant BMP receptor, $ ALK3^{QD} $, and administered these cells to immunocompromised mice. Further characterization was performed in vitro to address the role of activated BMP signalling on the EOC phenotype, with particular emphasis on epithelial-mesenchymal transition (EMT) and cell adhesion. Results Unexpectedly, doxycycline-induced $ ALK3^{QD} $ expression in OVCA429 cells reduced tumour implantation on peritoneal surfaces and ascites formation when xenografted into immunocompromised mice by intraperitoneal injection. To determine the potential mechanisms controlling this in vivo observation, we followed with several cell culture experiments. Doxycycline-induced $ ALK3^{QD} $ expression enhanced the refractile, spindle-shaped morphology of cultured OVCA429 cells eliciting an EMT-like response. Using in vitro wound healing assays, we observed that $ ALK3^{QD} $-expressing cells migrated with long, cytoplasmic projections extending into the wound space. The phenotypic alterations of $ ALK3^{QD} $-expressing cells correlated with changes in specific gene expression patterns of EMT, including increased Snail and Slug and reduced E-cadherin mRNA expression. In addition, $ ALK3^{QD} $ signalling reduced β1- and β3-integrin expression, critical molecules involved in ovarian cancer cell adhesion. The combination of reduced E-cadherin and β-integrin expression correlates directly with the reduced EOC cell cohesion in spheroids and reduced cell adhesion to the extracellular matrix substrates fibronectin and vitronectin that was observed. Conclusions We propose that the key steps of ovarian cancer metastasis, specifically cell cohesion of multicellular aggregates in ascites and cell adhesion for reattachment to secondary sites, may be inhibited by overactive BMP signalling, thereby decreasing the ultimate malignant potential of ovarian cancer in this model system. | ||
| 650 | 4 | |a Epithelial Ovarian Cancer |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a OVCA429 Cell |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Ovarian Surface Epithelial |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Bone Morphogenetic Protein Signalling |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Epithelial Ovarian Cancer Cell |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Mujoomdar, Michelle L |4 aut | |
| 700 | 1 | |a Nachtigal, Mark W |4 aut | |
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10.1186/1757-2215-3-5 doi (DE-627)SPR029664373 (SPR)1757-2215-3-5-e DE-627 ger DE-627 rakwb eng Shepherd, Trevor G verfasserin aut Constitutive activation of BMP signalling abrogates experimental metastasis of OVCA429 cells via reduced cell adhesion 2010 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Shepherd et al; licensee BioMed Central Ltd. 2010 Background Activation of bone morphogenetic protein (BMP)4 signalling in human ovarian cancer cells induces a number of phenotypic changes in vitro, including altered cell morphology, adhesion, motility and invasion, relative to normal human ovarian surface epithelial cells. From these in vitro analyses, we had hypothesized that active BMP signalling promotes the metastatic potential of ovarian cancer. Methods To test this directly, we engineered OVCA429 human ovarian cancer cells possessing doxycycline-inducible expression of a constitutively-active mutant BMP receptor, $ ALK3^{QD} $, and administered these cells to immunocompromised mice. Further characterization was performed in vitro to address the role of activated BMP signalling on the EOC phenotype, with particular emphasis on epithelial-mesenchymal transition (EMT) and cell adhesion. Results Unexpectedly, doxycycline-induced $ ALK3^{QD} $ expression in OVCA429 cells reduced tumour implantation on peritoneal surfaces and ascites formation when xenografted into immunocompromised mice by intraperitoneal injection. To determine the potential mechanisms controlling this in vivo observation, we followed with several cell culture experiments. Doxycycline-induced $ ALK3^{QD} $ expression enhanced the refractile, spindle-shaped morphology of cultured OVCA429 cells eliciting an EMT-like response. Using in vitro wound healing assays, we observed that $ ALK3^{QD} $-expressing cells migrated with long, cytoplasmic projections extending into the wound space. The phenotypic alterations of $ ALK3^{QD} $-expressing cells correlated with changes in specific gene expression patterns of EMT, including increased Snail and Slug and reduced E-cadherin mRNA expression. In addition, $ ALK3^{QD} $ signalling reduced β1- and β3-integrin expression, critical molecules involved in ovarian cancer cell adhesion. The combination of reduced E-cadherin and β-integrin expression correlates directly with the reduced EOC cell cohesion in spheroids and reduced cell adhesion to the extracellular matrix substrates fibronectin and vitronectin that was observed. Conclusions We propose that the key steps of ovarian cancer metastasis, specifically cell cohesion of multicellular aggregates in ascites and cell adhesion for reattachment to secondary sites, may be inhibited by overactive BMP signalling, thereby decreasing the ultimate malignant potential of ovarian cancer in this model system. Epithelial Ovarian Cancer (dpeaa)DE-He213 OVCA429 Cell (dpeaa)DE-He213 Ovarian Surface Epithelial (dpeaa)DE-He213 Bone Morphogenetic Protein Signalling (dpeaa)DE-He213 Epithelial Ovarian Cancer Cell (dpeaa)DE-He213 Mujoomdar, Michelle L aut Nachtigal, Mark W aut Enthalten in Journal of ovarian research London : BioMed Central, 2008 3(2010), 1 vom: 26. Feb. (DE-627)581041070 (DE-600)2455679-8 1757-2215 nnns volume:3 year:2010 number:1 day:26 month:02 https://dx.doi.org/10.1186/1757-2215-3-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 3 2010 1 26 02 |
| spelling |
10.1186/1757-2215-3-5 doi (DE-627)SPR029664373 (SPR)1757-2215-3-5-e DE-627 ger DE-627 rakwb eng Shepherd, Trevor G verfasserin aut Constitutive activation of BMP signalling abrogates experimental metastasis of OVCA429 cells via reduced cell adhesion 2010 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Shepherd et al; licensee BioMed Central Ltd. 2010 Background Activation of bone morphogenetic protein (BMP)4 signalling in human ovarian cancer cells induces a number of phenotypic changes in vitro, including altered cell morphology, adhesion, motility and invasion, relative to normal human ovarian surface epithelial cells. From these in vitro analyses, we had hypothesized that active BMP signalling promotes the metastatic potential of ovarian cancer. Methods To test this directly, we engineered OVCA429 human ovarian cancer cells possessing doxycycline-inducible expression of a constitutively-active mutant BMP receptor, $ ALK3^{QD} $, and administered these cells to immunocompromised mice. Further characterization was performed in vitro to address the role of activated BMP signalling on the EOC phenotype, with particular emphasis on epithelial-mesenchymal transition (EMT) and cell adhesion. Results Unexpectedly, doxycycline-induced $ ALK3^{QD} $ expression in OVCA429 cells reduced tumour implantation on peritoneal surfaces and ascites formation when xenografted into immunocompromised mice by intraperitoneal injection. To determine the potential mechanisms controlling this in vivo observation, we followed with several cell culture experiments. Doxycycline-induced $ ALK3^{QD} $ expression enhanced the refractile, spindle-shaped morphology of cultured OVCA429 cells eliciting an EMT-like response. Using in vitro wound healing assays, we observed that $ ALK3^{QD} $-expressing cells migrated with long, cytoplasmic projections extending into the wound space. The phenotypic alterations of $ ALK3^{QD} $-expressing cells correlated with changes in specific gene expression patterns of EMT, including increased Snail and Slug and reduced E-cadherin mRNA expression. In addition, $ ALK3^{QD} $ signalling reduced β1- and β3-integrin expression, critical molecules involved in ovarian cancer cell adhesion. The combination of reduced E-cadherin and β-integrin expression correlates directly with the reduced EOC cell cohesion in spheroids and reduced cell adhesion to the extracellular matrix substrates fibronectin and vitronectin that was observed. Conclusions We propose that the key steps of ovarian cancer metastasis, specifically cell cohesion of multicellular aggregates in ascites and cell adhesion for reattachment to secondary sites, may be inhibited by overactive BMP signalling, thereby decreasing the ultimate malignant potential of ovarian cancer in this model system. Epithelial Ovarian Cancer (dpeaa)DE-He213 OVCA429 Cell (dpeaa)DE-He213 Ovarian Surface Epithelial (dpeaa)DE-He213 Bone Morphogenetic Protein Signalling (dpeaa)DE-He213 Epithelial Ovarian Cancer Cell (dpeaa)DE-He213 Mujoomdar, Michelle L aut Nachtigal, Mark W aut Enthalten in Journal of ovarian research London : BioMed Central, 2008 3(2010), 1 vom: 26. Feb. (DE-627)581041070 (DE-600)2455679-8 1757-2215 nnns volume:3 year:2010 number:1 day:26 month:02 https://dx.doi.org/10.1186/1757-2215-3-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 3 2010 1 26 02 |
| allfields_unstemmed |
10.1186/1757-2215-3-5 doi (DE-627)SPR029664373 (SPR)1757-2215-3-5-e DE-627 ger DE-627 rakwb eng Shepherd, Trevor G verfasserin aut Constitutive activation of BMP signalling abrogates experimental metastasis of OVCA429 cells via reduced cell adhesion 2010 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Shepherd et al; licensee BioMed Central Ltd. 2010 Background Activation of bone morphogenetic protein (BMP)4 signalling in human ovarian cancer cells induces a number of phenotypic changes in vitro, including altered cell morphology, adhesion, motility and invasion, relative to normal human ovarian surface epithelial cells. From these in vitro analyses, we had hypothesized that active BMP signalling promotes the metastatic potential of ovarian cancer. Methods To test this directly, we engineered OVCA429 human ovarian cancer cells possessing doxycycline-inducible expression of a constitutively-active mutant BMP receptor, $ ALK3^{QD} $, and administered these cells to immunocompromised mice. Further characterization was performed in vitro to address the role of activated BMP signalling on the EOC phenotype, with particular emphasis on epithelial-mesenchymal transition (EMT) and cell adhesion. Results Unexpectedly, doxycycline-induced $ ALK3^{QD} $ expression in OVCA429 cells reduced tumour implantation on peritoneal surfaces and ascites formation when xenografted into immunocompromised mice by intraperitoneal injection. To determine the potential mechanisms controlling this in vivo observation, we followed with several cell culture experiments. Doxycycline-induced $ ALK3^{QD} $ expression enhanced the refractile, spindle-shaped morphology of cultured OVCA429 cells eliciting an EMT-like response. Using in vitro wound healing assays, we observed that $ ALK3^{QD} $-expressing cells migrated with long, cytoplasmic projections extending into the wound space. The phenotypic alterations of $ ALK3^{QD} $-expressing cells correlated with changes in specific gene expression patterns of EMT, including increased Snail and Slug and reduced E-cadherin mRNA expression. In addition, $ ALK3^{QD} $ signalling reduced β1- and β3-integrin expression, critical molecules involved in ovarian cancer cell adhesion. The combination of reduced E-cadherin and β-integrin expression correlates directly with the reduced EOC cell cohesion in spheroids and reduced cell adhesion to the extracellular matrix substrates fibronectin and vitronectin that was observed. Conclusions We propose that the key steps of ovarian cancer metastasis, specifically cell cohesion of multicellular aggregates in ascites and cell adhesion for reattachment to secondary sites, may be inhibited by overactive BMP signalling, thereby decreasing the ultimate malignant potential of ovarian cancer in this model system. Epithelial Ovarian Cancer (dpeaa)DE-He213 OVCA429 Cell (dpeaa)DE-He213 Ovarian Surface Epithelial (dpeaa)DE-He213 Bone Morphogenetic Protein Signalling (dpeaa)DE-He213 Epithelial Ovarian Cancer Cell (dpeaa)DE-He213 Mujoomdar, Michelle L aut Nachtigal, Mark W aut Enthalten in Journal of ovarian research London : BioMed Central, 2008 3(2010), 1 vom: 26. Feb. (DE-627)581041070 (DE-600)2455679-8 1757-2215 nnns volume:3 year:2010 number:1 day:26 month:02 https://dx.doi.org/10.1186/1757-2215-3-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 3 2010 1 26 02 |
| allfieldsGer |
10.1186/1757-2215-3-5 doi (DE-627)SPR029664373 (SPR)1757-2215-3-5-e DE-627 ger DE-627 rakwb eng Shepherd, Trevor G verfasserin aut Constitutive activation of BMP signalling abrogates experimental metastasis of OVCA429 cells via reduced cell adhesion 2010 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Shepherd et al; licensee BioMed Central Ltd. 2010 Background Activation of bone morphogenetic protein (BMP)4 signalling in human ovarian cancer cells induces a number of phenotypic changes in vitro, including altered cell morphology, adhesion, motility and invasion, relative to normal human ovarian surface epithelial cells. From these in vitro analyses, we had hypothesized that active BMP signalling promotes the metastatic potential of ovarian cancer. Methods To test this directly, we engineered OVCA429 human ovarian cancer cells possessing doxycycline-inducible expression of a constitutively-active mutant BMP receptor, $ ALK3^{QD} $, and administered these cells to immunocompromised mice. Further characterization was performed in vitro to address the role of activated BMP signalling on the EOC phenotype, with particular emphasis on epithelial-mesenchymal transition (EMT) and cell adhesion. Results Unexpectedly, doxycycline-induced $ ALK3^{QD} $ expression in OVCA429 cells reduced tumour implantation on peritoneal surfaces and ascites formation when xenografted into immunocompromised mice by intraperitoneal injection. To determine the potential mechanisms controlling this in vivo observation, we followed with several cell culture experiments. Doxycycline-induced $ ALK3^{QD} $ expression enhanced the refractile, spindle-shaped morphology of cultured OVCA429 cells eliciting an EMT-like response. Using in vitro wound healing assays, we observed that $ ALK3^{QD} $-expressing cells migrated with long, cytoplasmic projections extending into the wound space. The phenotypic alterations of $ ALK3^{QD} $-expressing cells correlated with changes in specific gene expression patterns of EMT, including increased Snail and Slug and reduced E-cadherin mRNA expression. In addition, $ ALK3^{QD} $ signalling reduced β1- and β3-integrin expression, critical molecules involved in ovarian cancer cell adhesion. The combination of reduced E-cadherin and β-integrin expression correlates directly with the reduced EOC cell cohesion in spheroids and reduced cell adhesion to the extracellular matrix substrates fibronectin and vitronectin that was observed. Conclusions We propose that the key steps of ovarian cancer metastasis, specifically cell cohesion of multicellular aggregates in ascites and cell adhesion for reattachment to secondary sites, may be inhibited by overactive BMP signalling, thereby decreasing the ultimate malignant potential of ovarian cancer in this model system. Epithelial Ovarian Cancer (dpeaa)DE-He213 OVCA429 Cell (dpeaa)DE-He213 Ovarian Surface Epithelial (dpeaa)DE-He213 Bone Morphogenetic Protein Signalling (dpeaa)DE-He213 Epithelial Ovarian Cancer Cell (dpeaa)DE-He213 Mujoomdar, Michelle L aut Nachtigal, Mark W aut Enthalten in Journal of ovarian research London : BioMed Central, 2008 3(2010), 1 vom: 26. Feb. (DE-627)581041070 (DE-600)2455679-8 1757-2215 nnns volume:3 year:2010 number:1 day:26 month:02 https://dx.doi.org/10.1186/1757-2215-3-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 3 2010 1 26 02 |
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10.1186/1757-2215-3-5 doi (DE-627)SPR029664373 (SPR)1757-2215-3-5-e DE-627 ger DE-627 rakwb eng Shepherd, Trevor G verfasserin aut Constitutive activation of BMP signalling abrogates experimental metastasis of OVCA429 cells via reduced cell adhesion 2010 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Shepherd et al; licensee BioMed Central Ltd. 2010 Background Activation of bone morphogenetic protein (BMP)4 signalling in human ovarian cancer cells induces a number of phenotypic changes in vitro, including altered cell morphology, adhesion, motility and invasion, relative to normal human ovarian surface epithelial cells. From these in vitro analyses, we had hypothesized that active BMP signalling promotes the metastatic potential of ovarian cancer. Methods To test this directly, we engineered OVCA429 human ovarian cancer cells possessing doxycycline-inducible expression of a constitutively-active mutant BMP receptor, $ ALK3^{QD} $, and administered these cells to immunocompromised mice. Further characterization was performed in vitro to address the role of activated BMP signalling on the EOC phenotype, with particular emphasis on epithelial-mesenchymal transition (EMT) and cell adhesion. Results Unexpectedly, doxycycline-induced $ ALK3^{QD} $ expression in OVCA429 cells reduced tumour implantation on peritoneal surfaces and ascites formation when xenografted into immunocompromised mice by intraperitoneal injection. To determine the potential mechanisms controlling this in vivo observation, we followed with several cell culture experiments. Doxycycline-induced $ ALK3^{QD} $ expression enhanced the refractile, spindle-shaped morphology of cultured OVCA429 cells eliciting an EMT-like response. Using in vitro wound healing assays, we observed that $ ALK3^{QD} $-expressing cells migrated with long, cytoplasmic projections extending into the wound space. The phenotypic alterations of $ ALK3^{QD} $-expressing cells correlated with changes in specific gene expression patterns of EMT, including increased Snail and Slug and reduced E-cadherin mRNA expression. In addition, $ ALK3^{QD} $ signalling reduced β1- and β3-integrin expression, critical molecules involved in ovarian cancer cell adhesion. The combination of reduced E-cadherin and β-integrin expression correlates directly with the reduced EOC cell cohesion in spheroids and reduced cell adhesion to the extracellular matrix substrates fibronectin and vitronectin that was observed. Conclusions We propose that the key steps of ovarian cancer metastasis, specifically cell cohesion of multicellular aggregates in ascites and cell adhesion for reattachment to secondary sites, may be inhibited by overactive BMP signalling, thereby decreasing the ultimate malignant potential of ovarian cancer in this model system. Epithelial Ovarian Cancer (dpeaa)DE-He213 OVCA429 Cell (dpeaa)DE-He213 Ovarian Surface Epithelial (dpeaa)DE-He213 Bone Morphogenetic Protein Signalling (dpeaa)DE-He213 Epithelial Ovarian Cancer Cell (dpeaa)DE-He213 Mujoomdar, Michelle L aut Nachtigal, Mark W aut Enthalten in Journal of ovarian research London : BioMed Central, 2008 3(2010), 1 vom: 26. Feb. (DE-627)581041070 (DE-600)2455679-8 1757-2215 nnns volume:3 year:2010 number:1 day:26 month:02 https://dx.doi.org/10.1186/1757-2215-3-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 3 2010 1 26 02 |
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Constitutive activation of BMP signalling abrogates experimental metastasis of OVCA429 cells via reduced cell adhesion Epithelial Ovarian Cancer (dpeaa)DE-He213 OVCA429 Cell (dpeaa)DE-He213 Ovarian Surface Epithelial (dpeaa)DE-He213 Bone Morphogenetic Protein Signalling (dpeaa)DE-He213 Epithelial Ovarian Cancer Cell (dpeaa)DE-He213 |
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Constitutive activation of BMP signalling abrogates experimental metastasis of OVCA429 cells via reduced cell adhesion |
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Background Activation of bone morphogenetic protein (BMP)4 signalling in human ovarian cancer cells induces a number of phenotypic changes in vitro, including altered cell morphology, adhesion, motility and invasion, relative to normal human ovarian surface epithelial cells. From these in vitro analyses, we had hypothesized that active BMP signalling promotes the metastatic potential of ovarian cancer. Methods To test this directly, we engineered OVCA429 human ovarian cancer cells possessing doxycycline-inducible expression of a constitutively-active mutant BMP receptor, $ ALK3^{QD} $, and administered these cells to immunocompromised mice. Further characterization was performed in vitro to address the role of activated BMP signalling on the EOC phenotype, with particular emphasis on epithelial-mesenchymal transition (EMT) and cell adhesion. Results Unexpectedly, doxycycline-induced $ ALK3^{QD} $ expression in OVCA429 cells reduced tumour implantation on peritoneal surfaces and ascites formation when xenografted into immunocompromised mice by intraperitoneal injection. To determine the potential mechanisms controlling this in vivo observation, we followed with several cell culture experiments. Doxycycline-induced $ ALK3^{QD} $ expression enhanced the refractile, spindle-shaped morphology of cultured OVCA429 cells eliciting an EMT-like response. Using in vitro wound healing assays, we observed that $ ALK3^{QD} $-expressing cells migrated with long, cytoplasmic projections extending into the wound space. The phenotypic alterations of $ ALK3^{QD} $-expressing cells correlated with changes in specific gene expression patterns of EMT, including increased Snail and Slug and reduced E-cadherin mRNA expression. In addition, $ ALK3^{QD} $ signalling reduced β1- and β3-integrin expression, critical molecules involved in ovarian cancer cell adhesion. The combination of reduced E-cadherin and β-integrin expression correlates directly with the reduced EOC cell cohesion in spheroids and reduced cell adhesion to the extracellular matrix substrates fibronectin and vitronectin that was observed. Conclusions We propose that the key steps of ovarian cancer metastasis, specifically cell cohesion of multicellular aggregates in ascites and cell adhesion for reattachment to secondary sites, may be inhibited by overactive BMP signalling, thereby decreasing the ultimate malignant potential of ovarian cancer in this model system. © Shepherd et al; licensee BioMed Central Ltd. 2010 |
| abstractGer |
Background Activation of bone morphogenetic protein (BMP)4 signalling in human ovarian cancer cells induces a number of phenotypic changes in vitro, including altered cell morphology, adhesion, motility and invasion, relative to normal human ovarian surface epithelial cells. From these in vitro analyses, we had hypothesized that active BMP signalling promotes the metastatic potential of ovarian cancer. Methods To test this directly, we engineered OVCA429 human ovarian cancer cells possessing doxycycline-inducible expression of a constitutively-active mutant BMP receptor, $ ALK3^{QD} $, and administered these cells to immunocompromised mice. Further characterization was performed in vitro to address the role of activated BMP signalling on the EOC phenotype, with particular emphasis on epithelial-mesenchymal transition (EMT) and cell adhesion. Results Unexpectedly, doxycycline-induced $ ALK3^{QD} $ expression in OVCA429 cells reduced tumour implantation on peritoneal surfaces and ascites formation when xenografted into immunocompromised mice by intraperitoneal injection. To determine the potential mechanisms controlling this in vivo observation, we followed with several cell culture experiments. Doxycycline-induced $ ALK3^{QD} $ expression enhanced the refractile, spindle-shaped morphology of cultured OVCA429 cells eliciting an EMT-like response. Using in vitro wound healing assays, we observed that $ ALK3^{QD} $-expressing cells migrated with long, cytoplasmic projections extending into the wound space. The phenotypic alterations of $ ALK3^{QD} $-expressing cells correlated with changes in specific gene expression patterns of EMT, including increased Snail and Slug and reduced E-cadherin mRNA expression. In addition, $ ALK3^{QD} $ signalling reduced β1- and β3-integrin expression, critical molecules involved in ovarian cancer cell adhesion. The combination of reduced E-cadherin and β-integrin expression correlates directly with the reduced EOC cell cohesion in spheroids and reduced cell adhesion to the extracellular matrix substrates fibronectin and vitronectin that was observed. Conclusions We propose that the key steps of ovarian cancer metastasis, specifically cell cohesion of multicellular aggregates in ascites and cell adhesion for reattachment to secondary sites, may be inhibited by overactive BMP signalling, thereby decreasing the ultimate malignant potential of ovarian cancer in this model system. © Shepherd et al; licensee BioMed Central Ltd. 2010 |
| abstract_unstemmed |
Background Activation of bone morphogenetic protein (BMP)4 signalling in human ovarian cancer cells induces a number of phenotypic changes in vitro, including altered cell morphology, adhesion, motility and invasion, relative to normal human ovarian surface epithelial cells. From these in vitro analyses, we had hypothesized that active BMP signalling promotes the metastatic potential of ovarian cancer. Methods To test this directly, we engineered OVCA429 human ovarian cancer cells possessing doxycycline-inducible expression of a constitutively-active mutant BMP receptor, $ ALK3^{QD} $, and administered these cells to immunocompromised mice. Further characterization was performed in vitro to address the role of activated BMP signalling on the EOC phenotype, with particular emphasis on epithelial-mesenchymal transition (EMT) and cell adhesion. Results Unexpectedly, doxycycline-induced $ ALK3^{QD} $ expression in OVCA429 cells reduced tumour implantation on peritoneal surfaces and ascites formation when xenografted into immunocompromised mice by intraperitoneal injection. To determine the potential mechanisms controlling this in vivo observation, we followed with several cell culture experiments. Doxycycline-induced $ ALK3^{QD} $ expression enhanced the refractile, spindle-shaped morphology of cultured OVCA429 cells eliciting an EMT-like response. Using in vitro wound healing assays, we observed that $ ALK3^{QD} $-expressing cells migrated with long, cytoplasmic projections extending into the wound space. The phenotypic alterations of $ ALK3^{QD} $-expressing cells correlated with changes in specific gene expression patterns of EMT, including increased Snail and Slug and reduced E-cadherin mRNA expression. In addition, $ ALK3^{QD} $ signalling reduced β1- and β3-integrin expression, critical molecules involved in ovarian cancer cell adhesion. The combination of reduced E-cadherin and β-integrin expression correlates directly with the reduced EOC cell cohesion in spheroids and reduced cell adhesion to the extracellular matrix substrates fibronectin and vitronectin that was observed. Conclusions We propose that the key steps of ovarian cancer metastasis, specifically cell cohesion of multicellular aggregates in ascites and cell adhesion for reattachment to secondary sites, may be inhibited by overactive BMP signalling, thereby decreasing the ultimate malignant potential of ovarian cancer in this model system. © Shepherd et al; licensee BioMed Central Ltd. 2010 |
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