PUBLICATION
Lactate secreted by glycolytic conjunctival melanoma cells attracts and polarizes macrophages to drive angiogenesis in zebrafish xenografts
- Authors
- Yin, J., Forn-Cuní, G., Surendran, A.M., Lopes-Bastos, B., Pouliopoulou, N., Jager, M.J., Le Dévédec, S.E., Chen, Q., Snaar-Jagalska, B.E.
- ID
- ZDB-PUB-240607-5
- Date
- 2024
- Source
- Angiogenesis 27(4): 703-717 (Journal)
- Registered Authors
- Snaar-Jagalska, Ewa B.
- Keywords
- Angiogenesis, Conjunctival melanoma, Glycolysis, Lactate, Macrophages, Zebrafish model
- MeSH Terms
-
- Zebrafish*/metabolism
- Heterografts
- Neovascularization, Pathologic*/metabolism
- Neovascularization, Pathologic*/pathology
- Lactic Acid*/metabolism
- Conjunctival Neoplasms*/blood supply
- Conjunctival Neoplasms*/metabolism
- Conjunctival Neoplasms*/pathology
- Macrophages*/metabolism
- Macrophages*/pathology
- Cell Line, Tumor
- Animals
- Glycolysis*
- Tumor Microenvironment
- Melanoma*/blood supply
- Melanoma*/metabolism
- Melanoma*/pathology
- Angiogenesis
- Humans
- PubMed
- 38842752 Full text @ Angiogenesis
Citation
Yin, J., Forn-Cuní, G., Surendran, A.M., Lopes-Bastos, B., Pouliopoulou, N., Jager, M.J., Le Dévédec, S.E., Chen, Q., Snaar-Jagalska, B.E. (2024) Lactate secreted by glycolytic conjunctival melanoma cells attracts and polarizes macrophages to drive angiogenesis in zebrafish xenografts. Angiogenesis. 27(4):703-717.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping