{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T03:54:05Z","timestamp":1793850845210,"version":"4.6.1"},"reference-count":38,"publisher":"American Association for Cancer Research (AACR)","issue":"9","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Dissemination of tumor cells is an essential step in metastasis. Direct contact between a macrophage, mammalian-enabled (MENA)\u2013overexpressing tumor cell, and endothelial cell [Tumor MicroEnvironment of Metastasis (TMEM)] correlates with metastasis in breast cancer patients. Here we show, using intravital high-resolution two-photon microscopy, that transient vascular permeability and tumor cell intravasation occur simultaneously and exclusively at TMEM. The hyperpermeable nature of tumor vasculature is described as spatially and temporally heterogeneous. Using real-time imaging, we observed that vascular permeability is transient, restricted to the TMEM, and required for tumor cell dissemination. VEGFA signaling from TIE2hi TMEM macrophages causes local loss of vascular junctions, transient vascular permeability, and tumor cell intravasation, demonstrating a role for the TMEM within the primary mammary tumor. These data provide insight into the mechanism of tumor cell intravasation and vascular permeability in breast cancer, explaining the value of TMEM density as a predictor of distant metastatic recurrence in patients.<\/jats:p>\n                  <jats:p>Significance: Tumor vasculature is abnormal with increased permeability. Here, we show that VEGFA signaling from TIE2hi TMEM macrophages results in local, transient vascular permeability and tumor cell intravasation. These data provide evidence for the mechanism underlying the association of TMEM with distant metastatic recurrence, offering a rationale for therapies targeting TMEM. Cancer Discov; 5(9); 932\u201343. \u00a92015 AACR.<\/jats:p>\n                  <jats:p>See related commentary by Kadioglu and De Palma, p. 906.<\/jats:p>\n                  <jats:p>This article is highlighted in the In This Issue feature, p. 893<\/jats:p>","DOI":"10.1158\/2159-8290.cd-15-0012","type":"journal-article","created":{"date-parts":[[2015,8,12]],"date-time":"2015-08-12T20:29:03Z","timestamp":1439411343000},"page":"932-943","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":605,"title":["Real-Time Imaging Reveals Local, Transient Vascular Permeability, and Tumor Cell Intravasation Stimulated by TIE2hi Macrophage\u2013Derived VEGFA"],"prefix":"10.1158","volume":"5","author":[{"given":"Allison S.","family":"Harney","sequence":"first","affiliation":[{"name":"1Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, New York, New York."},{"name":"2Department of Radiology, Albert Einstein College of Medicine, New York, New York."},{"name":"3Integrated Imaging Program, Albert Einstein College of Medicine, New York, New York."},{"name":"4Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther N.","family":"Arwert","sequence":"additional","affiliation":[{"name":"1Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, New York, New York."},{"name":"4Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, New York, New York."},{"name":"5Tumour Cell Biology Laboratory, Cancer Research UK, London Research Institute, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Entenberg","sequence":"additional","affiliation":[{"name":"1Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, New York, New York."},{"name":"3Integrated Imaging Program, Albert Einstein College of Medicine, New York, New York."},{"name":"4Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yarong","family":"Wang","sequence":"additional","affiliation":[{"name":"1Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, New York, New York."},{"name":"4Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Guo","sequence":"additional","affiliation":[{"name":"1Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, New York, New York."},{"name":"4Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin-Zhi","family":"Qian","sequence":"additional","affiliation":[{"name":"6Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, New York."},{"name":"7Department of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine, New York, New York."},{"name":"8MRC Center for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja H.","family":"Oktay","sequence":"additional","affiliation":[{"name":"9Department of Pathology, Albert Einstein College of Medicine, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey W.","family":"Pollard","sequence":"additional","affiliation":[{"name":"6Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, New York."},{"name":"7Department of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine, New York, New York."},{"name":"8MRC Center for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan G.","family":"Jones","sequence":"additional","affiliation":[{"name":"1Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, New York, New York."},{"name":"3Integrated Imaging Program, Albert Einstein College of Medicine, New York, New York."},{"name":"9Department of Pathology, Albert Einstein College of Medicine, New York, New York."},{"name":"10Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Condeelis","sequence":"additional","affiliation":[{"name":"1Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, New York, New York."},{"name":"3Integrated Imaging Program, Albert Einstein College of Medicine, New York, New York."},{"name":"4Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, New York, 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