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Histologically, MBC presents with increased microvessels beneath the parietal and visceral pleura, indicating generalized angiogenic activity. Breast cancer\u2010associated pleural fluid (BAPF) was collected and cultured with HUVECs to recapitulate the molecular changes in subpleural endothelial cells. The clinical progression of triple\u2010negative breast cancer (TNBC) is much more aggressive than that of hormone receptor\u2010positive breast cancer (HPBC). However, BAPF from HPBC (BAPF\u2010HP) and TNBC (BAPF\u2010TN) homogeneously induced endothelial proliferation, migration, and angiogenesis. In addition, BAPF elicited negligible changes in the protein marker of endothelial\u2010mesenchymal transition. Both BAPF\u2010HP and BAPF\u2010TN exclusively upregulated JNK signaling among all MAPKs in HUVECs. By contrast, the response to the JNK inhibitor was insignificant in Transwell and tube formation assays of the HUVECs cultured with BAPF\u2010TN. The distinct contribution of p\u2010JNK to endothelial angiogenesis was consequently thought to be induced by BAPF\u2010HP and BAPF\u2010TN. Due to increased angiogenic factors in HUVECs cultured with BAPF, vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor was applied accordingly. Responses to VEGFR2 blockade were observed in both BAPF\u2010HP and BAPF\u2010TN concerning endothelial migration and angiogenesis. In conclusion, the above results revealed microvessel formation in the pleura of MBC and the underlying activation of p\u2010JNK\/VEGFR2 signaling. Distinct responses to blocking p\u2010JNK and VEGFR2 in HUVECs cultured with BAPF\u2010HP or BAPF\u2010TN could lay the groundwork for future investigations in treating MBC based on hormone receptor status.<\/jats:p>","DOI":"10.1111\/cas.14772","type":"journal-article","created":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T01:49:21Z","timestamp":1607996961000},"page":"781-791","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Distinct JNK\/VEGFR signaling on angiogenesis of breast cancer\u2010associated pleural fluid based on hormone receptor status"],"prefix":"10.1111","volume":"112","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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsin\u2010Han","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Biology and Anatomy National Defense Medical Center Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming\u2010Shen","family":"Dai","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Tri\u2010Service General Hospital National Defense Medical Center Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen\u2010Chiuan","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tri\u2010Service General Hospital National Defense Medical Center Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming\u2010Sheng","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Taichung Armed Force General Hospital Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li\u2010Ting","family":"Cheng","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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herng\u2010Sheng","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Kaohsiung Veterans General Hospital Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biology and Anatomy National Defense Medical Center Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9783-5423","authenticated-orcid":false,"given":"Chen\u2010Liang","family":"Tsai","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":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,1,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00171610"},{"key":"e_1_2_9_3_1","unstructured":"AndersCK CareyLA BursteinHJ.ER\/PR negative HER2\u2010negative (triple\u2010negative) breast cancer. 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