{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T17:02:07Z","timestamp":1784739727206,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T00:00:00Z","timestamp":1597190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital","doi-asserted-by":"publisher","award":["TSGH\u2010C108\u2010109"],"award-info":[{"award-number":["TSGH\u2010C108\u2010109"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 107\u20102320\u2010B\u2010016\u2010011\u2010MY3"],"award-info":[{"award-number":["MOST 107\u20102320\u2010B\u2010016\u2010011\u2010MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Malignant pleural effusion (MPE) and paramalignant pleural effusion (PPE) remain debilitating complications in lung cancer patients with poor prognosis and limited treatment options. The role of vascular endothelial cells has not been explored in the pleural environment of lung cancer. By integrating MPE and PPE as malignant\u2010associated pleural fluid (MAPF), the current study aimed to evaluate the effect of MAPF on cell proliferation, migration and angiogenesis of HUVEC. First, increased capillaries were identified in the subpleural layer of lung adenocarcinoma. Compatible with pathological observations, the ubiquitous elevation of HUVEC survival was identified in MAPF culture regardless of the underlying cancer type, the driver gene mutation, prior treatments and evidence of malignant cells in pleural fluid. Moreover, MAPF enhanced HUVEC motility with the formation of lamellipodia and filopodia and focal adhesion complex. Tube formation assay revealed angiogenic behavior with the observation of sheet\u2010like structures. HUVEC cultured with MAPF resulted in a significant increase in MAPK phosphorylation. Accompanied with VEGFR2 upregulation in MAPF culture, there was increased expressions of p\u2010STAT3, HIF\u20101\u03b1 and Nf\u2010kB. VEGF\/VEGFR2 blockade regressed endothelial migration and angiogenesis but not cell proliferation. Our data indicate the angiogenic activities of MAPF on vascular endothelial cells that revealed increased pleural capillaries in lung cancer. Targeting the VEGF\/VEGFR2 pathway might modulate the angiogenic propensity of MAPF in future clinical investigations.<\/jats:p>","DOI":"10.1111\/cas.14584","type":"journal-article","created":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T10:19:13Z","timestamp":1595585953000},"page":"3747-3758","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Effect of malignant\u2010associated pleural effusion on endothelial viability, motility and angiogenesis in lung cancer"],"prefix":"10.1111","volume":"111","author":[{"given":"Chih\u2010Ying","family":"Changchien","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Tri\u2010Service General Hospital, National Defense Medical Center Taipei Taiwan"},{"name":"Department of Biology and Anatomy National Defense Medical Center Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6303-5858","authenticated-orcid":false,"given":"Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biology and Anatomy National Defense Medical Center Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin\u2010Han","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Biology and Anatomy National Defense Medical Center Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan\u2010Yueh","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Department of Internal Medicine Tri\u2010Service General Hospital, National Defense Medical Center Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Chiuan","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Pathology Tri\u2010Service General Hospital, National Defense Medical Center Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao\u2010Chung","family":"Tsai","sequence":"additional","affiliation":[{"name":"Division of Chest Medicine Department of Internal Medicine Tri\u2010Service General Hospital Songshan Branch, National Defense Medical Center Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chieh\u2010Yung","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Department of Internal Medicine Tri\u2010Service General Hospital, National Defense Medical Center Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herng\u2010Sheng","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Kaohsiung Veterans General Hospital Kaohsiung 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