{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:03:48Z","timestamp":1789549428698,"version":"build-2803163510"},"reference-count":32,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T00:00:00Z","timestamp":1629072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003711","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["109-2320-B-001 -019 -MY3"],"award-info":[{"award-number":["109-2320-B-001 -019 -MY3"]}],"id":[{"id":"10.13039\/501100003711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003711","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 106-2320-B-001-004-MY3"],"award-info":[{"award-number":["MOST 106-2320-B-001-004-MY3"]}],"id":[{"id":"10.13039\/501100003711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Current conventional cancer therapies for melanoma brain metastasis (MBM) remain ineffective. In this study, we demonstrated the bioefficacy of a phyto-glyceroglycolipid, 1,2-di-O-\u03b1-linolenoyl-3-O-\u03b2-galactopyranosyl-sn-glycerol (dLGG) alone, or in combination with liposomal doxorubicin (Lip-DOX) or Avastin against MBM in a syngeneic B16BM4COX\u22122\/Luc brain-seeking melanoma mouse model. Treatment with dLGG\u201310, dLGG\u201325, dLGG\u201310 + Avastin\u20135, Lipo-DOX\u20132, dLGG\u201310 + Lipo-DOX\u20132 or Lipo-DOX\u20132 + Avastin\u20135 suppressed, respectively, 17.9%, 59.1%, 55.7%, 16.2%, 44.5% and 72.4% of MBM in mice relative to the untreated tumor control. Metastatic PD-L1+ melanoma cells, infiltration of M2-like macrophages and CD31+ endothelial cells, and high expression levels of 15-LOX\/CYP450 4A enzymes in the brain tumor microenvironment of the tumor control mice were significantly attenuated in dLGG-treated mice; conversely, M1-like resident microglia and cytotoxic T cells were increased. A lipidomics study showed that dLGG promoted B16BM4 cells to secrete oxylipins 9,10-\/12,13-EpOMEs into the culture medium. Furthermore, the conditioned medium of B16BM4 cells pretreated with dLGG or 9,10-EpOMEs + 12,13-EpOMEs drove M2-like macrophages to polarize into M1-like macrophages in vitro. An ex vivo 3D-culture assay further demonstrated that dLGG, 9,10-EpOME or 9,10-EpOME + 12,13-EpOME pretreatment attenuated B16BM4 cells invading brain tissue, and prevented microglia\/macrophages infiltrating into the interface of melanoma plug and brain organ\/tissue. In summary, this report provides a novel therapeutic strategy and mechanistic insights into phytogalactolipid dLGG for combating MBM.<\/jats:p>","DOI":"10.3390\/cancers13164120","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T21:27:45Z","timestamp":1629149265000},"page":"4120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Phytogalactolipid dLGG Inhibits Mouse Melanoma Brain Metastasis through Regulating Oxylipin Activity and Re-Programming Macrophage Polarity in the Tumor Microenvironment"],"prefix":"10.3390","volume":"13","author":[{"given":"Chung-Chih","family":"Yang","sequence":"first","affiliation":[{"name":"Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 115, Taiwan"},{"name":"Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Ting","family":"Chang","sequence":"additional","affiliation":[{"name":"Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan"},{"name":"Department of Biochemical Science and Technology, National Taiwan University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Kuei","family":"Chang","sequence":"additional","affiliation":[{"name":"Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 115, Taiwan"},{"name":"Department of Neurosurgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lie-Fen","family":"Shyur","sequence":"additional","affiliation":[{"name":"Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 115, Taiwan"},{"name":"Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan"},{"name":"Department of Biochemical Science and Technology, National Taiwan University, Taipei 110, Taiwan"},{"name":"Ph.D. Program in Translational Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1056\/NEJMoa1805453","article-title":"Combined nivolumab and ipilimumab in melanoma metastatic to the brain","volume":"379","author":"Tawbi","year":"2018","journal-title":"N. 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