Lactate secreted by glycolytic conjunctival melanoma cells attracts and polarizes macrophages to drive angiogenesis in zebrafish xenografts.

Autor: Yin J; Institute of Biology, Leiden University, Leiden, 2333 BE, The Netherlands., Forn-Cuní G; Institute of Biology, Leiden University, Leiden, 2333 BE, The Netherlands., Surendran AM; Institute of Biology, Leiden University, Leiden, 2333 BE, The Netherlands., Lopes-Bastos B; Institute of Biology, Leiden University, Leiden, 2333 BE, The Netherlands., Pouliopoulou N; Institute of Biology, Leiden University, Leiden, 2333 BE, The Netherlands., Jager MJ; Department of Ophthalmology, Leiden University Medical Center, Leiden, 2333 ZA, the Netherlands., Le Dévédec SE; Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University, Leiden, 2333 BE, The Netherlands., Chen Q; Institute of Biology, Leiden University, Leiden, 2333 BE, The Netherlands. quanchichen@njglyy.com.; Division of Spine Surgery, Department of Orthopedic Surgery, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing University, Nanjing, 210008, China. quanchichen@njglyy.com., Snaar-Jagalska BE; Institute of Biology, Leiden University, Leiden, 2333 BE, The Netherlands. b.e.snaar-jagalska@biology.leidenuniv.nl.
Jazyk: angličtina
Zdroj: Angiogenesis [Angiogenesis] 2024 Nov; Vol. 27 (4), pp. 703-717. Date of Electronic Publication: 2024 Jun 06.
DOI: 10.1007/s10456-024-09930-y
Abstrakt: Conjunctival melanoma (CoM) is a rare but potentially lethal cancer of the eye, with limited therapeutic option for metastases. A better understanding how primary CoM disseminate to form metastases is urgently needed in order to develop novel therapies. Previous studies indicated that primary CoM tumors express Vascular Endothelial Growth Factor (VEGF) and may recruit pro-tumorigenic M2-like macrophages. However, due to a lack of proper models, the expected role of angiogenesis in the metastatic dissemination of CoM is still unknown. We show that cells derived from two CoM cell lines induce a strong angiogenic response when xenografted in zebrafish larvae. CoM cells are highly glycolytic and secrete lactate, which recruits and polarizes human and zebrafish macrophages towards a M2-like phenotype. These macrophages elevate the levels of proangiogenic factors such as VEGF, TGF-β, and IL-10 in the tumor microenvironment to induce an angiogenic response towards the engrafted CoM cells in vivo. Chemical ablation of zebrafish macrophages or inhibition of glycolysis in CoM cells terminates this response, suggesting that attraction of lactate-dependent macrophages into engrafted CoM cells drives angiogenesis and serves as a possible dissemination mechanism for glycolytic CoM cells.
Competing Interests: Declarations Informed consent statement All animal experiments were approved by the Animal Experiments Committee (Dier Experimenten Commissie, D.E.C.) under licenses AVD1060020172410 and AVD10600202216495. All animals were maintained in accordance with local guidelines using standard protocols: www.ZFIN.org (accessed on 12 Dec 2019). Competing interests The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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