{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:29:20Z","timestamp":1791584960718,"version":"4.3.4"},"reference-count":65,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T00:00:00Z","timestamp":1661126400000},"content-version":"vor","delay-in-days":233,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>\n                    Hypoxia\u2010induced M2 phenotypes of tumor associated macrophages (TAMs) promote the development and chemoresistance of multiple types of cancers, including glioblastoma (GBM). However, the detailed molecular mechanisms have not been fully understood. In this study, we firstly reported that hypoxic pressure promoted M2 macrophage generation, which further promoted cancer progression and temozolomide (TMZ) resistance in GBM through secreting vascular endothelial growth factor (VEGF). Specifically, the clinical data suggested that M2 macrophages were significantly enriched in GBM tissues compared with the adjacent normal tissues, and the following\n                    <jats:italic>in vitro<\/jats:italic>\n                    experiments validated that hypoxic pressure promoted M2\u2010polarized macrophages through upregulating hypoxia\u2010inducible factor\u20101\n                    <jats:italic>\u03b1<\/jats:italic>\n                    (HIF\u20101\n                    <jats:italic>\u03b1<\/jats:italic>\n                    ). In addition, hypoxic M2 macrophages VEGF\u2010dependently promoted cell proliferation, epithelial\u2010mesenchymal transition (EMT), glioblastoma stem cell (GSC) properties, and TMZ resistance in GBM cells through activating the PI3K\/Akt\/Nrf2 pathway. Also, M2 macrophages secreted VEGF to accelerate angiogenesis in human umbilical vein endothelial cells (HUVECs) through interacting with its receptor VEGFR. In general, we concluded that hypoxic M2 macrophages contributed to cancer progression, stemness, drug resistance, and angiogenesis in GBM through secreting VEGF, and our data supported the notion that targeting hypoxia\u2010associated M2 macrophages might be an effective treatment strategy for GBM in clinical practices.\n                  <\/jats:p>","DOI":"10.1155\/2022\/1614336","type":"journal-article","created":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T19:50:23Z","timestamp":1661197823000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Hypoxia\u2010Driven M2\u2010Polarized Macrophages Facilitate Cancer Aggressiveness and Temozolomide Resistance in 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