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Ortho- and Ectopic Zebrafish Xeno-Engraftment of Ocular Melanoma to Recapitulate Primary Tumor and Experimental Metastasis Development
Published on: September 4, 2021
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Lactate secreted by glycolytic conjunctival melanoma cells attracts and polarizes macrophages to drive angiogenesis
Jie Yin1, Gabriel Forn-Cuní1, Akshaya Mahalakshmi Surendran1
1Institute of Biology, Leiden University, Leiden, 2333 BE, The Netherlands.
Angiogenesis
|June 6, 2024
Summary
Conjunctival melanoma cells secrete lactate, which recruits M2 macrophages. These macrophages promote blood vessel growth, potentially aiding cancer cell spread and metastasis.
Area of Science:
- Ophthalmology
- Cancer Biology
- Immunology
Background:
- Conjunctival melanoma (CoM) is a rare eye cancer with limited treatment options for metastasis.
- Understanding CoM metastasis is crucial for developing new therapies.
- The role of angiogenesis in CoM dissemination is unclear due to a lack of suitable models.
Purpose of the Study:
- To investigate the role of angiogenesis and macrophage recruitment in conjunctival melanoma metastasis.
- To explore the mechanisms by which CoM cells interact with their microenvironment to promote dissemination.
Main Methods:
- Xenografting of CoM cell lines into zebrafish larvae.
- Analysis of macrophage recruitment and polarization.
- Assessment of angiogenic responses in vivo.
- Inhibition of glycolysis and macrophage ablation.
Main Results:
- CoM cells induced significant angiogenesis when xenografted in zebrafish.
- CoM cells are highly glycolytic, secreting lactate that recruits and polarizes macrophages to an M2-like phenotype.
- Macrophages elevated pro-angiogenic factors (VEGF, TGF-β, IL-10), driving angiogenesis towards CoM cells.
- Inhibiting glycolysis or ablating macrophages halted the angiogenic response.
Conclusions:
- Lactate secreted by CoM cells attracts and polarizes macrophages, promoting angiogenesis.
- This macrophage-mediated angiogenesis is a potential mechanism for CoM cell dissemination and metastasis.
- Targeting CoM cell glycolysis or macrophage activity may offer novel therapeutic strategies.
