Thrombocytes Correlate with Lymphangiogenesis in Human Esophageal Cancer and Mediate Growth of Lymphatic Endothelial Cells In Vitro
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{"title"=>"Thrombocytes Correlate with Lymphangiogenesis in Human Esophageal Cancer and Mediate Growth of Lymphatic Endothelial Cells In Vitro", "type"=>"journal", "authors"=>[{"first_name"=>"Sebastian F.", "last_name"=>"Schoppmann", "scopus_author_id"=>"6603369899"}, {"first_name"=>"Lejla", "last_name"=>"Alidzanovic", "scopus_author_id"=>"50160918600"}, {"first_name"=>"Andrea", "last_name"=>"Schultheis", "scopus_author_id"=>"37027119200"}, {"first_name"=>"Thomas", "last_name"=>"Perkmann", "scopus_author_id"=>"8904629500"}, {"first_name"=>"Christine", "last_name"=>"Brostjan", "scopus_author_id"=>"6603958624"}, {"first_name"=>"Peter", "last_name"=>"Birner", "scopus_author_id"=>"7005495248"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84879476490", "sgr"=>"84879476490", "pui"=>"369200469", "isbn"=>"1932-6203", "pmid"=>"23840559", "doi"=>"10.1371/journal.pone.0066941"}, "id"=>"aca6b33c-aa8d-3cf2-bec1-917108ff6fa9", "abstract"=>"Recent data provide evidence for an important role of thrombocytes in lymphangiogenesis within human malignant disease. The aim of this study was to investigate the role of thrombocytes in lymphangiogenesis in human esophageal cancer. Perioperative peripheral blood platelet counts (PBPC) were evaluated retrospectively in 320 patients with esophageal cancer, comprising 184 adenocarcinomas (AC), and 136 squamous cell carcinomas (SCC). Data on lymphangiogenesis evaluated by anti-podoplanin immunostaining were available from previous studies, platelets within the tumor tissue were assessed by CD61 immunostaining. For in vitro studies, human lymphatic endothelial cells (LECs) were isolated and co-cultured with peripheral blood platelets. Stromal thrombocytic clusters (STC) were evident in 82 samples (25.6%), and vascular thrombocytic clusters (VTC) in 56 (17.5%). STC and VTC were associated with a significantly higher PBPC at investigation of all cases. The presence of STC was associated with higher lymphatic microvessel density (p<0.001), PBPC and STC were associated with lymphovascular invasion of tumor cells in a regression model. The presence of STCs was associated with shorter DFS of all patients (p = 0.036, Breslow test), and VTC with shorter DFS in in SCC (p = 0.025, Breslow test). In cell culture, LEC proliferation was enhanced by co-culture with human platelets in a dose- and time-dependent manner mediated by the release of PDGF-BB and VEGF-C. Platelets play an important role in lymphangiogenesis and lymphovascular invasion in esophageal cancer, influencing prognosis. So the disruption of signaling pathways between platelets, tumor cells and lymphatic endothelium might be of benefit for patients.", "link"=>"http://www.mendeley.com/research/thrombocytes-correlate-lymphangiogenesis-human-esophageal-cancer-mediate-growth-lymphatic-endothelia", "reader_count"=>9, "reader_count_by_academic_status"=>{"Researcher"=>1, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Student > Master"=>3, "Other"=>2}, "reader_count_by_user_role"=>{"Researcher"=>1, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Student > Master"=>3, "Other"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>7, "Agricultural and Biological Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1102035"], "description"=>"<p>A: LEC proliferation is enhanced by co-culture with human platelets in a dose-dependent manner. LECs were seeded at 1×10∧5 per 30 mm well. After 24 hours isolated platelets were added at 3×10∧7, 10∧6 or 10∧5 per well and cells were cultured for another 48 h. For quantification of cell proliferation, the LEC count was determined (black bars, right scale) and metabolic activity was measured by tetrazolium reduction assay (white bars, left scale). B–E: Corresponding microscopic images to A: B: Control; C: EC+Px10∧7, D: EC+Px10∧6, E: EC+Px10∧5. F: LEC proliferation is enhanced by co-culture with human platelets in a time-dependent manner. LECs were seeded at 1×10∧5 per 30 mm well. 24 hours thereafter isolated platelets were added at 1×10∧7 per well and cells were cultured for another 24, 48 and 72 hours. Cell counts were determined for LEC-platelet co-cultures (solid line) as compared to LECs without platelet addition (dashed line). G+H: Growth factor release during co-culture of LECs and human platelets. LECs were seeded at 1×10∧5 per 30 mm well. After 24 hours isolated platelets were added at 7×10∧7, 10∧6 or 10∧5 per well and cells were cultured for another 48 h. Culture supernatant was harvested, centrifuged (to remove cellular components) and then assayed for the concentration of PDGF-BB (G) and VEGF-C (H) by enzyme-linked immunosorbent assay. I: Platelet-induced LEC proliferation is mediated by PDGFRβ, VEGFR-2 and -3. LECs were seeded at 1×10∧5 per 30 mm well. After 24 hours isolated platelets were added at 7×10∧7 per well with or without blocking reagents against PDGFRß, VEGFR-2 and/or VEGFR-3. Cells were cultured for another 48 h before determining LEC counts.</p>", "links"=>[], "tags"=>["Population biology", "epidemiology", "Clinical research design", "Cancer epidemiology", "Gastroenterology and hepatology", "esophagus", "Gastrointestinal cancers", "hematology", "platelets", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Esophageal cancer", "Basic cancer research", "Cancer risk factors"], "article_id"=>732264, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Sebastian F. Schoppmann", "Lejla Alidzanovic", "Andrea Schultheis", "Thomas Perkmann", "Christine Brostjan", "Peter Birner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066941.g003", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cell_culture_experiments_/732264", "title"=>"Cell culture experiments.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-26 08:56:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/1102036"], "description"=>"<p>Clinical data of patients and presence of stromal and vascular thrombocytic clusters.</p>", "links"=>[], "tags"=>["Population biology", "epidemiology", "Clinical research design", "Cancer epidemiology", "Gastroenterology and hepatology", "esophagus", "Gastrointestinal cancers", "hematology", "platelets", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Esophageal cancer", "Basic cancer research", "Cancer risk factors", "patients", "stromal", "vascular", "thrombocytic"], "article_id"=>732265, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Sebastian F. Schoppmann", "Lejla Alidzanovic", "Andrea Schultheis", "Thomas Perkmann", "Christine Brostjan", "Peter Birner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066941.t001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_data_of_patients_and_presence_of_stromal_and_vascular_thrombocytic_clusters_/732265", "title"=>"Clinical data of patients and presence of stromal and vascular thrombocytic clusters.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-26 08:56:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/1102037"], "description"=>"<p>univariate survival analysis of patients age was performed using univariate Cox regression.</p>*<p>AC was associated with significantly better prognosis in multivariate analysis than SCC.</p>", "links"=>[], "tags"=>["Population biology", "epidemiology", "Clinical research design", "Cancer epidemiology", "Gastroenterology and hepatology", "esophagus", "Gastrointestinal cancers", "hematology", "platelets", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Esophageal cancer", "Basic cancer research", "Cancer risk factors"], "article_id"=>732266, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Sebastian F. Schoppmann", "Lejla Alidzanovic", "Andrea Schultheis", "Thomas Perkmann", "Christine Brostjan", "Peter Birner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066941.t002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Survival_Analysis_/732266", "title"=>"Survival Analysis.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-26 08:56:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/1102033"], "description"=>"<p>A: Vascular thrombocytic cluster (VTC) in an esophageal cancer specimen (original magnification x400). B: Stromal thrombocytic cluster (STC) in an esophageal cancer specimen assessed by anti – CD61 immunostaining (original magnification x400). C: Esophageal cancer specimen with high lymphatic microvessel density (LMVD) assessed by anti- podoplanin immunostaining (original magnification x200). D: Lymphovascular invasion of tumor cells assessed by anti-podoplanin immunostaining (original magnification x200). E: Double staining for lymphatic vessels using (red, anti-podoplanin) and thrombocytes (brown, anti- CD61) (original magnification x400). F–H: Error bars showing mean values±2× standard error. Peripheral blood platelet counts (PBPC) were significantly higher in samples with VTC (F). PBPC (G) and LMVD (H) were significantly higher in esophageal cancer samples with STC.</p>", "links"=>[], "tags"=>["Population biology", "epidemiology", "Clinical research design", "Cancer epidemiology", "Gastroenterology and hepatology", "esophagus", "Gastrointestinal cancers", "hematology", "platelets", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Esophageal cancer", "Basic cancer research", "Cancer risk factors"], "article_id"=>732262, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Sebastian F. Schoppmann", "Lejla Alidzanovic", "Andrea Schultheis", "Thomas Perkmann", "Christine Brostjan", "Peter Birner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066941.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Samples_and_results_of_immunohistochemistry_/732262", "title"=>"Samples and results of immunohistochemistry.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-26 08:56:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/1102034"], "description"=>"<p><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066941#pone-0066941-g002\" target=\"_blank\">Fig.2A:</a> Presence of stromal thrombocytic clusters (STC) was associated with shorter DFS in all cases. At investigation of tumor types separately, STC was associated with shorter DFS in squamous cell cancer (SCC) (Fig. 2B) as well as in adenocarcinoma (AC) (Fig. 2C). Fig. 2D: Presence of vascular thrombocytic clusters (VTC) was associated with shorter DFS in SCC. Fig. 2E: Surprisingly, VTC was associated with significantly longer DFS in AC in multivariate analysis. Nevertheless, note that only relatively few events are seen in the VTC+ curve, and curves are crossing each other over, qualifying this finding. Fig. 2F: VTC was associated with shorter OS in SCC.</p>", "links"=>[], "tags"=>["Population biology", "epidemiology", "Clinical research design", "Cancer epidemiology", "Gastroenterology and hepatology", "esophagus", "Gastrointestinal cancers", "hematology", "platelets", "oncology", "Cancers and neoplasms", "Gastrointestinal tumors", "Esophageal cancer", "Basic cancer research", "Cancer risk factors", "meier", "curves", "esophageal", "cancer"], "article_id"=>732263, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Sebastian F. Schoppmann", "Lejla Alidzanovic", "Andrea Schultheis", "Thomas Perkmann", "Christine Brostjan", "Peter Birner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066941.g002", "stats"=>{"downloads"=>2, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Kaplan_Meier_curves_of_disease_free_DFS_and_overall_survival_OS_of_esophageal_cancer_patients_/732263", "title"=>"Kaplan Meier curves of disease free (DFS) and overall survival (OS) of esophageal cancer patients.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-26 08:56:20"}

PMC Usage Stats | Further Information

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Relative Metric

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