Thrombotic characteristics of extracellular vesicles derived from prostate cancer cells
Background Prostate cancer (PC) patients in advanced stages of the disease have high risk of blood coagulation complications. The procoagulant molecule Tissue factor (TF), and the fibrinolysis inhibitor plasminogen activator inhibitor‐1 PAI‐1 play important role in this complication. Extracellular v...
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| Veröffentlicht in: | The Prostate 2018-09, Vol.78 (13), p.953-961 |
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| creator | Al Saleh, Hassan A. Haas‐Neill, Sandor Al‐Hashimi, Ali Kapoor, Anil Shayegan, Bobby Austin, Richard C. Al‐Nedawi, Khalid |
| description | Background
Prostate cancer (PC) patients in advanced stages of the disease have high risk of blood coagulation complications. The procoagulant molecule Tissue factor (TF), and the fibrinolysis inhibitor plasminogen activator inhibitor‐1 PAI‐1 play important role in this complication. Extracellular vesicles (EV) shed from cancer cells may contribute to the regulation of TF and PAI‐1. The procoagulant activity of EV can be associated with the oncogenic and metastatic characteristics of their cells.
Methods
We have expressed EGFRvIII in DU145 cells to assess the role of this oncogene in the procoagulant activity of EV. The intercellular exchange of TF via EV was assessed by downregulating its expression in DU145 cells using shRNA vector, and determining the transfer of TF via EV enriched with the protein. Two PC cell lines with different metastatic potential were used to assess the correlation between the procoagulant activity of EV and the metastatic potential of PC cells. Photometric assays were used to determine FXa‐activity and thrombin generation as indicators for the procoagulant activity of EV. Double‐tagged proteinase‐activated receptor 1(PAR‐1) expressed in CHO cells to assess its activation by EV.
Results
The expression of EGFRvIII in DU145 cells led to increased mRNA levels for TF and PAI‐1, but the increase in these proteins expression was detected mostly in the EV. EV with enhanced levels of TF protein conferred higher TF procoagulant activity on the acceptor cells by intercellular exchange of this protein. Procoagulant activity of EV, assessed by FXa activity, and thrombin generation, was correlated with the oncogenic and metastatic potential of PC cells. The ability of EV to generate thrombin led to the activation of PAR‐1, which was evident by the truncation of tagged‐PAR‐1.
Conclusion
The active oncogene EGFRvIII increases the concentration of TF and PAI‐1 in EV. The procoagulant activity of EV is associated with the oncogenic and metastatic characteristics of their PC cells. Also, EV may contribute to the high procoagulant activity in the tumour microenvironment by the intercellular exchange of TF. Finally, through the generation of thrombin, EV can activate PAR‐1, which evidently contributes to cancer progression, linking the coagulation system to tumor progression. |
| doi_str_mv | 10.1002/pros.23653 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2039296709</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2084299858</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3573-40188933519e5ec876f004d01dc932278bb0f9c20fb82ee2ad3daf31dee7b68b3</originalsourceid><addsrcrecordid>eNp90E9LwzAYBvAgipvTix9AAl5E6HyTrE1ylOE_ECY68VjS9C3r6NaZtNN9e1M3PXjwFBJ-efLkJeSUwZAB8KuVq_2QiyQWe6TPQMsIYBTvkz5wCdGICdkjR97PAQIHfkh6XMuExZz3ydt05upFVjelpXZmnLENutKHrad1QfGzCUdYVW1lHF2jL22FnubBrDGnRbhLu-cb0yC1ZmnR0Y77Y3JQmMrjyW4dkNfbm-n4Pnqc3D2Mrx8jK2IpohEwpbQQMdMYo1UyKUL3HFhuteBcqiyDQlsORaY4Ije5yE0hWI4os0RlYkAutrmhxXuLvkkXpe8amCXWrU85CM11IkEHev6HzuvWLUO7oNSIa61iFdTlVtnwLe-wSFeuXBi3SRmk3bjT7r_p97gDPttFttkC81_6M98A2BZ8lBVu_olKn54nL9vQLwTGi2A</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2084299858</pqid></control><display><type>article</type><title>Thrombotic characteristics of extracellular vesicles derived from prostate cancer cells</title><source>Wiley Online Library Journals Frontfile Complete</source><creator>Al Saleh, Hassan A. ; Haas‐Neill, Sandor ; Al‐Hashimi, Ali ; Kapoor, Anil ; Shayegan, Bobby ; Austin, Richard C. ; Al‐Nedawi, Khalid</creator><creatorcontrib>Al Saleh, Hassan A. ; Haas‐Neill, Sandor ; Al‐Hashimi, Ali ; Kapoor, Anil ; Shayegan, Bobby ; Austin, Richard C. ; Al‐Nedawi, Khalid</creatorcontrib><description>Background
Prostate cancer (PC) patients in advanced stages of the disease have high risk of blood coagulation complications. The procoagulant molecule Tissue factor (TF), and the fibrinolysis inhibitor plasminogen activator inhibitor‐1 PAI‐1 play important role in this complication. Extracellular vesicles (EV) shed from cancer cells may contribute to the regulation of TF and PAI‐1. The procoagulant activity of EV can be associated with the oncogenic and metastatic characteristics of their cells.
Methods
We have expressed EGFRvIII in DU145 cells to assess the role of this oncogene in the procoagulant activity of EV. The intercellular exchange of TF via EV was assessed by downregulating its expression in DU145 cells using shRNA vector, and determining the transfer of TF via EV enriched with the protein. Two PC cell lines with different metastatic potential were used to assess the correlation between the procoagulant activity of EV and the metastatic potential of PC cells. Photometric assays were used to determine FXa‐activity and thrombin generation as indicators for the procoagulant activity of EV. Double‐tagged proteinase‐activated receptor 1(PAR‐1) expressed in CHO cells to assess its activation by EV.
Results
The expression of EGFRvIII in DU145 cells led to increased mRNA levels for TF and PAI‐1, but the increase in these proteins expression was detected mostly in the EV. EV with enhanced levels of TF protein conferred higher TF procoagulant activity on the acceptor cells by intercellular exchange of this protein. Procoagulant activity of EV, assessed by FXa activity, and thrombin generation, was correlated with the oncogenic and metastatic potential of PC cells. The ability of EV to generate thrombin led to the activation of PAR‐1, which was evident by the truncation of tagged‐PAR‐1.
Conclusion
The active oncogene EGFRvIII increases the concentration of TF and PAI‐1 in EV. The procoagulant activity of EV is associated with the oncogenic and metastatic characteristics of their PC cells. Also, EV may contribute to the high procoagulant activity in the tumour microenvironment by the intercellular exchange of TF. Finally, through the generation of thrombin, EV can activate PAR‐1, which evidently contributes to cancer progression, linking the coagulation system to tumor progression.</description><identifier>ISSN: 0270-4137</identifier><identifier>EISSN: 1097-0045</identifier><identifier>DOI: 10.1002/pros.23653</identifier><identifier>PMID: 29761522</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Blood coagulation ; exosomes ; Extracellular vesicles ; Fibrinolysis ; fibrynolysis ; Metastases ; Metastasis ; microvesicles ; mRNA ; PAI‐1 ; Pheochromocytoma cells ; Plasminogen activator inhibitors ; Prostate cancer ; Proteinase ; Proteins ; Thrombin ; Tissue factor ; Tumor microenvironment ; Tumors</subject><ispartof>The Prostate, 2018-09, Vol.78 (13), p.953-961</ispartof><rights>2018 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3573-40188933519e5ec876f004d01dc932278bb0f9c20fb82ee2ad3daf31dee7b68b3</citedby><cites>FETCH-LOGICAL-c3573-40188933519e5ec876f004d01dc932278bb0f9c20fb82ee2ad3daf31dee7b68b3</cites><orcidid>0000-0001-5140-3799</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpros.23653$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpros.23653$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,778,782,1414,27907,27908,45557,45558</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29761522$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Al Saleh, Hassan A.</creatorcontrib><creatorcontrib>Haas‐Neill, Sandor</creatorcontrib><creatorcontrib>Al‐Hashimi, Ali</creatorcontrib><creatorcontrib>Kapoor, Anil</creatorcontrib><creatorcontrib>Shayegan, Bobby</creatorcontrib><creatorcontrib>Austin, Richard C.</creatorcontrib><creatorcontrib>Al‐Nedawi, Khalid</creatorcontrib><title>Thrombotic characteristics of extracellular vesicles derived from prostate cancer cells</title><title>The Prostate</title><addtitle>Prostate</addtitle><description>Background
Prostate cancer (PC) patients in advanced stages of the disease have high risk of blood coagulation complications. The procoagulant molecule Tissue factor (TF), and the fibrinolysis inhibitor plasminogen activator inhibitor‐1 PAI‐1 play important role in this complication. Extracellular vesicles (EV) shed from cancer cells may contribute to the regulation of TF and PAI‐1. The procoagulant activity of EV can be associated with the oncogenic and metastatic characteristics of their cells.
Methods
We have expressed EGFRvIII in DU145 cells to assess the role of this oncogene in the procoagulant activity of EV. The intercellular exchange of TF via EV was assessed by downregulating its expression in DU145 cells using shRNA vector, and determining the transfer of TF via EV enriched with the protein. Two PC cell lines with different metastatic potential were used to assess the correlation between the procoagulant activity of EV and the metastatic potential of PC cells. Photometric assays were used to determine FXa‐activity and thrombin generation as indicators for the procoagulant activity of EV. Double‐tagged proteinase‐activated receptor 1(PAR‐1) expressed in CHO cells to assess its activation by EV.
Results
The expression of EGFRvIII in DU145 cells led to increased mRNA levels for TF and PAI‐1, but the increase in these proteins expression was detected mostly in the EV. EV with enhanced levels of TF protein conferred higher TF procoagulant activity on the acceptor cells by intercellular exchange of this protein. Procoagulant activity of EV, assessed by FXa activity, and thrombin generation, was correlated with the oncogenic and metastatic potential of PC cells. The ability of EV to generate thrombin led to the activation of PAR‐1, which was evident by the truncation of tagged‐PAR‐1.
Conclusion
The active oncogene EGFRvIII increases the concentration of TF and PAI‐1 in EV. The procoagulant activity of EV is associated with the oncogenic and metastatic characteristics of their PC cells. Also, EV may contribute to the high procoagulant activity in the tumour microenvironment by the intercellular exchange of TF. Finally, through the generation of thrombin, EV can activate PAR‐1, which evidently contributes to cancer progression, linking the coagulation system to tumor progression.</description><subject>Blood coagulation</subject><subject>exosomes</subject><subject>Extracellular vesicles</subject><subject>Fibrinolysis</subject><subject>fibrynolysis</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>microvesicles</subject><subject>mRNA</subject><subject>PAI‐1</subject><subject>Pheochromocytoma cells</subject><subject>Plasminogen activator inhibitors</subject><subject>Prostate cancer</subject><subject>Proteinase</subject><subject>Proteins</subject><subject>Thrombin</subject><subject>Tissue factor</subject><subject>Tumor microenvironment</subject><subject>Tumors</subject><issn>0270-4137</issn><issn>1097-0045</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp90E9LwzAYBvAgipvTix9AAl5E6HyTrE1ylOE_ECY68VjS9C3r6NaZtNN9e1M3PXjwFBJ-efLkJeSUwZAB8KuVq_2QiyQWe6TPQMsIYBTvkz5wCdGICdkjR97PAQIHfkh6XMuExZz3ydt05upFVjelpXZmnLENutKHrad1QfGzCUdYVW1lHF2jL22FnubBrDGnRbhLu-cb0yC1ZmnR0Y77Y3JQmMrjyW4dkNfbm-n4Pnqc3D2Mrx8jK2IpohEwpbQQMdMYo1UyKUL3HFhuteBcqiyDQlsORaY4Ije5yE0hWI4os0RlYkAutrmhxXuLvkkXpe8amCXWrU85CM11IkEHev6HzuvWLUO7oNSIa61iFdTlVtnwLe-wSFeuXBi3SRmk3bjT7r_p97gDPttFttkC81_6M98A2BZ8lBVu_olKn54nL9vQLwTGi2A</recordid><startdate>201809</startdate><enddate>201809</enddate><creator>Al Saleh, Hassan A.</creator><creator>Haas‐Neill, Sandor</creator><creator>Al‐Hashimi, Ali</creator><creator>Kapoor, Anil</creator><creator>Shayegan, Bobby</creator><creator>Austin, Richard C.</creator><creator>Al‐Nedawi, Khalid</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-5140-3799</orcidid></search><sort><creationdate>201809</creationdate><title>Thrombotic characteristics of extracellular vesicles derived from prostate cancer cells</title><author>Al Saleh, Hassan A. ; Haas‐Neill, Sandor ; Al‐Hashimi, Ali ; Kapoor, Anil ; Shayegan, Bobby ; Austin, Richard C. ; Al‐Nedawi, Khalid</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3573-40188933519e5ec876f004d01dc932278bb0f9c20fb82ee2ad3daf31dee7b68b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Blood coagulation</topic><topic>exosomes</topic><topic>Extracellular vesicles</topic><topic>Fibrinolysis</topic><topic>fibrynolysis</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>microvesicles</topic><topic>mRNA</topic><topic>PAI‐1</topic><topic>Pheochromocytoma cells</topic><topic>Plasminogen activator inhibitors</topic><topic>Prostate cancer</topic><topic>Proteinase</topic><topic>Proteins</topic><topic>Thrombin</topic><topic>Tissue factor</topic><topic>Tumor microenvironment</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Al Saleh, Hassan A.</creatorcontrib><creatorcontrib>Haas‐Neill, Sandor</creatorcontrib><creatorcontrib>Al‐Hashimi, Ali</creatorcontrib><creatorcontrib>Kapoor, Anil</creatorcontrib><creatorcontrib>Shayegan, Bobby</creatorcontrib><creatorcontrib>Austin, Richard C.</creatorcontrib><creatorcontrib>Al‐Nedawi, Khalid</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Prostate</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Al Saleh, Hassan A.</au><au>Haas‐Neill, Sandor</au><au>Al‐Hashimi, Ali</au><au>Kapoor, Anil</au><au>Shayegan, Bobby</au><au>Austin, Richard C.</au><au>Al‐Nedawi, Khalid</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Thrombotic characteristics of extracellular vesicles derived from prostate cancer cells</atitle><jtitle>The Prostate</jtitle><addtitle>Prostate</addtitle><date>2018-09</date><risdate>2018</risdate><volume>78</volume><issue>13</issue><spage>953</spage><epage>961</epage><pages>953-961</pages><issn>0270-4137</issn><eissn>1097-0045</eissn><abstract>Background
Prostate cancer (PC) patients in advanced stages of the disease have high risk of blood coagulation complications. The procoagulant molecule Tissue factor (TF), and the fibrinolysis inhibitor plasminogen activator inhibitor‐1 PAI‐1 play important role in this complication. Extracellular vesicles (EV) shed from cancer cells may contribute to the regulation of TF and PAI‐1. The procoagulant activity of EV can be associated with the oncogenic and metastatic characteristics of their cells.
Methods
We have expressed EGFRvIII in DU145 cells to assess the role of this oncogene in the procoagulant activity of EV. The intercellular exchange of TF via EV was assessed by downregulating its expression in DU145 cells using shRNA vector, and determining the transfer of TF via EV enriched with the protein. Two PC cell lines with different metastatic potential were used to assess the correlation between the procoagulant activity of EV and the metastatic potential of PC cells. Photometric assays were used to determine FXa‐activity and thrombin generation as indicators for the procoagulant activity of EV. Double‐tagged proteinase‐activated receptor 1(PAR‐1) expressed in CHO cells to assess its activation by EV.
Results
The expression of EGFRvIII in DU145 cells led to increased mRNA levels for TF and PAI‐1, but the increase in these proteins expression was detected mostly in the EV. EV with enhanced levels of TF protein conferred higher TF procoagulant activity on the acceptor cells by intercellular exchange of this protein. Procoagulant activity of EV, assessed by FXa activity, and thrombin generation, was correlated with the oncogenic and metastatic potential of PC cells. The ability of EV to generate thrombin led to the activation of PAR‐1, which was evident by the truncation of tagged‐PAR‐1.
Conclusion
The active oncogene EGFRvIII increases the concentration of TF and PAI‐1 in EV. The procoagulant activity of EV is associated with the oncogenic and metastatic characteristics of their PC cells. Also, EV may contribute to the high procoagulant activity in the tumour microenvironment by the intercellular exchange of TF. Finally, through the generation of thrombin, EV can activate PAR‐1, which evidently contributes to cancer progression, linking the coagulation system to tumor progression.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>29761522</pmid><doi>10.1002/pros.23653</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-5140-3799</orcidid></addata></record> |
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| subjects | Blood coagulation exosomes Extracellular vesicles Fibrinolysis fibrynolysis Metastases Metastasis microvesicles mRNA PAI‐1 Pheochromocytoma cells Plasminogen activator inhibitors Prostate cancer Proteinase Proteins Thrombin Tissue factor Tumor microenvironment Tumors |
| title | Thrombotic characteristics of extracellular vesicles derived from prostate cancer cells |
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