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

Ramos-Espinosa, Gustavo; Wang, Yuanyuan; Brandner, Johanna M.; Schneider, Stefan W.; Gorzelanny, Christian

doi:10.3390/ijms22083912

Submit to this Journal Review for this Journal Edit a Special Issue

Article Menu

...

Open AccessArticle

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

Gustavo Ramos-Espinosa

^†,

^†

and

Department of Dermatology and Venerology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany

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)

View Full-Text Download PDF

Browse Figures

Citation Export

Abstract

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

▼ Show Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Supplementary Material

Supplementary File 1:
ZIP-Document (ZIP, 5262 KiB)

Share and Cite

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

Find Other Styles

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Abstract views Pdf views Html views

Article Menu

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

Abstract

Supplementary Material

Share and Cite

Article Metrics

Article Access Statistics

Article Access Map by Country/Region

Further Information

Guidelines

MDPI Initiatives

Follow MDPI