{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T15:55:58Z","timestamp":1776095758970,"version":"3.50.1"},"reference-count":138,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T00:00:00Z","timestamp":1605139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/CVT\/276\/2020"],"award-info":[{"award-number":["UID\/CVT\/276\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The concept of tumor growth being angiogenesis dependent had its origin in the observations of Judah Folkman in 1969 of a retinoblastoma in a child. Tumor angiogenesis is initiated when endothelial cells (ECs) respond to local stimuli and migrate towards the growing mass, which results in the formation of tubular structures surrounded by perivascular support cells that transport blood to the inner tumor. In turn, the neo-vasculature supports tumor development and eventual metastasis. This process is highly regulated by several signaling pathways. Central to this process is the Notch signaling pathway. Beyond the role of Notch signaling in tumor angiogenesis, a major hallmark of cancer development, it has also been implicated in the regulation of tumor cell proliferation and survival, in epithelial-to-mesenchymal transition, invasion and metastasis and in the regulation of cancer stem cells, in a variety of hematologic and solid malignancies. There is increasing evidence for the tumor vasculature being important in roles other than those linked to blood perfusion. Namely, endothelial cells act on and influence neighboring tumor cells by use of angiocrine factors to generate a unique cellular microenvironment, thereby regulating tumor stem-like cells\u2019 homeostasis, modulating tumor progression, invasiveness, trafficking and metastasis. This review will focus on Notch signaling components that play a part in angiocrine signaling in a tumor setting.<\/jats:p>","DOI":"10.3390\/cells9112467","type":"journal-article","created":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T20:17:52Z","timestamp":1605212272000},"page":"2467","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Notch Signaling Function in the Angiocrine Regulation of Tumor Development"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3104-9259","authenticated-orcid":false,"given":"Alexandre","family":"Trindade","sequence":"first","affiliation":[{"name":"CIISA-Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, Avenida da Universidade T\u00e9cnica, 1300-477 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9255-3635","authenticated-orcid":false,"given":"Ant\u00f3nio","family":"Duarte","sequence":"additional","affiliation":[{"name":"CIISA-Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, Avenida da Universidade T\u00e9cnica, 1300-477 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,12]]},"reference":[{"key":"ref_1","unstructured":"Hunter, J. 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