In uveal melanoma, angiopoietin-2 but not angiopoietin-1 is increased in high-risk tumors, providing a potential druggable target

Anna M.W. Ten Voorde, Annemijn P.A. Wierenga, Rogier J. Nell, Pieter A. van der Velden, Gregorius P.M. Luyten, Robert M. Verdijk, Martine J. Jager*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Uveal melanoma (UM) metastasize haematogeneously, and tumor blood vessel density is an important prognostic factor. We hypothesized that proangiogenic factors such as angiopoietin-1 (ANG-1) and angiopoietin-2 (ANG-2), two targetable cytokines, might play a role in tumor development and metastatic behavior. mRNA levels of ANG-1 and ANG-2 were determined in 64 tumors using an Illumina HT-12 v4 mRNA chip and compared to clinical, pathologic, and genetic tumor parameters. Tissue expression was also determined by immunohistochemistry (IHC). Samples of aqueous humor were collected from 83 UM-containing enucleated eyes and protein levels that were determined in a multiplex proximity extension assay. High tissue gene expression of ANG-2, but not of ANG-1, was associated with high tumor thickness, high largest basal diameter, involvement of the ciliary body, and with UM-related death (ANG-2 mRNA p < 0.001; ANG-2 aqueous protein p < 0.001). The presence of the ANG-2 protein in aqueous humor correlated with its mRNA expression in the tumor (r = 0.309, p = 0.03). IHC showed that ANG-2 was expressed in macrophages as well as tumor cells. The presence of ANG-2 in the tumor and in aqueous humor, especially in high-risk tumors, make ANG-2 a potential targetable cytokine in uveal melanoma.

Original languageEnglish
Article number3986
JournalCancers
Volume13
Issue number16
DOIs
Publication statusPublished - 7 Aug 2021

Bibliographical note

Funding Information:
A.P.A.W., P.A.v.d.V., R.J.N. and M.J.J. were the recipients of a Horizon2020 CURE UM grant (667787) from the European Community.

Funding Information:
Acknowledgments: Supported by the European Commission, through Horizon 2020 Grant Cure UM (667787). We thank Thierry P.P. van den Bosch for his assistance in performing the IHC staining.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Fingerprint

Dive into the research topics of 'In uveal melanoma, angiopoietin-2 but not angiopoietin-1 is increased in high-risk tumors, providing a potential druggable target'. Together they form a unique fingerprint.

Cite this