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Article

Melanoma Associated Chitinase 3-Like 1 Promoted Endothelial Cell Activation and Immune Cell Recruitment

Department of Dermatology and Venerology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
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Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Mario Cioce
Int. J. Mol. Sci. 2021, 22(8), 3912; https://doi.org/10.3390/ijms22083912
Received: 17 March 2021 / Revised: 7 April 2021 / Accepted: 8 April 2021 / Published: 10 April 2021
(This article belongs to the Special Issue Tumor Secretome in Translational Oncology)
Chitinase 3-like 1 (CHI3L1) is an enzymatically inactive mammalian chitinase that is associated with tumor inflammation. Previous research indicated that CHI3L1 is able to interact with different extracellular matrix components, such as heparan sulfate. In the present work, we investigated whether the interaction of CHI3L1 with the extracellular matrix of melanoma cells can trigger an inflammatory activation of endothelial cells. The analysis of the melanoma cell secretome indicated that CHI3L1 increases the abundance of various cytokines, such as CC-chemokine ligand 2 (CCL2), and growth factors, such as vascular endothelial growth factor A (VEGF-A). Using a solid-phase binding assay, we found that heparan sulfate-bound VEGF-A and CCL2 were displaced by recombinant CHI3L1 in a dose-dependent manner. Microfluidic experiments indicated that the CHI3L1 altered melanoma cell secretome promoted immune cell recruitment to the vascular endothelium. In line with the elevated VEGF-A levels, CHI3L1 was also able to promote angiogenesis through the release of extracellular matrix-bound pro-angiogenic factors. In conclusion, we showed that CHI3L1 is able to affect the tumor cell secretome, which in turn can regulate immune cell recruitment and blood vessel formation. Accordingly, our data suggest that the molecular targeting of CHI3L1 in the course of cancer immunotherapies can tune patients’ response and antitumoral inflammation. View Full-Text
Keywords: YKL-40; glycosaminoglycan; extracellular matrix; endothelium YKL-40; glycosaminoglycan; extracellular matrix; endothelium
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MDPI and ACS Style

Ramos-Espinosa, G.; Wang, Y.; Brandner, J.M.; Schneider, S.W.; Gorzelanny, C. Melanoma Associated Chitinase 3-Like 1 Promoted Endothelial Cell Activation and Immune Cell Recruitment. Int. J. Mol. Sci. 2021, 22, 3912. https://doi.org/10.3390/ijms22083912

AMA Style

Ramos-Espinosa G, Wang Y, Brandner JM, Schneider SW, Gorzelanny C. Melanoma Associated Chitinase 3-Like 1 Promoted Endothelial Cell Activation and Immune Cell Recruitment. International Journal of Molecular Sciences. 2021; 22(8):3912. https://doi.org/10.3390/ijms22083912

Chicago/Turabian Style

Ramos-Espinosa, Gustavo, Yuanyuan Wang, Johanna M. Brandner, Stefan W. Schneider, and Christian Gorzelanny. 2021. "Melanoma Associated Chitinase 3-Like 1 Promoted Endothelial Cell Activation and Immune Cell Recruitment" International Journal of Molecular Sciences 22, no. 8: 3912. https://doi.org/10.3390/ijms22083912

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