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Extracellular vimentin mimics VEGF and is a target for anti-angiogenic immunotherapy

ABSTRACT: Anti-angiogenic anticancer therapies possess immune-stimulatory properties by counteracting pro-angiogenic molecular mechanisms. We report that tumor endothelial cells ubiquitously overexpress and secrete the intermediate filament protein vimentin through type III unconventional mechanisms. Extracellular vimentin is pro-angiogenic and functionally mimics VEGF action, while concomitantly acting as inhibitor of leukocyte-endothelial interactions. Targeting of extracellular vimentin presents a promising anti-angiogenic immunotherapy strategy against cancer. Here we describe profiling of the HUVEC (Human Umbilical Vein Endothelial Cell) proteome, with special emphasis on vimentin (variants) in the different fractions. We have evidence that vimentin is externalized and deposited in the matrix of cultured cells and is as such available for targeted antiangiogenic therapeutics. The aim of the experiment is to determine the protein variants of vimentin in the cell, the secretome, and in the matrix deposited by the cells.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Umbilical Vein

SUBMITTER: Sander Piersma

LAB HEAD: Connie Jimenez

PROVIDER: PXD024426 | Pride | 2022-03-29

REPOSITORIES: Pride

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Proteomic analysis of primary human microvascular endothelial cells (HMVECs) stimulated for 24â€‰h with either 50 ï�g/mL recombinant Fibrillin-1 C-terminal fragment or 25â€‰ng/ml VEGF-A compared to unstimulated cells.

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2023-05-31 | PXD029834 | Pride

βIV-spectrin as a stalk cell-intrinsic regulator of VEGF signaling

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2022-02-04 | PXD026618 | Pride

Analysis of the impact of DICER1 and DROSHA on the angio-genic capacity of human endothelial cells

Project description:RNAi-mediated knockdown of DICER1 and DROSHA, enzymes critically involved in miRNA biogenesis, has been postulated to affect the homeostasis and the angiogenic capacity of human endothelial cells. To re-evaluate this issue, we reduced the expression of DICER1 or DROSHA by RNAi-mediated knockdown and subsequently investigated the effect of these interventions on the angiogenic capacity of human umbilical vein endothelial cells (HUVEC) in vitro (proliferation, migration, tube formation, endothelial cell spheroid sprouting) and in a HUVEC xenograft assay in immune incompetent NSGTM mice in vivo. In contrast to previous reports, neither knockdown of DICER1 nor knockdown of DROSHA profoundly affected migration or tube formation of HUVEC or the angiogenic capacity of HUVEC in vivo. Furthermore, knockdown of DICER1 and the combined knockdown of DICER1 and DROSHA tended to increase VEGF-induced BrdU incorporation and induced angiogenic sprouting from HUVEC spheroids. Consistent with these observations, global proteomic analyses showed that knockdown of DICER1 or DROSHA only moderately altered HUVEC protein expression profiles but additively reduced, for example, expression of the angiogenesis inhibitor thrombospondin-1. In conclusion, global reduction of miRNA biogenesis by knockdown of DICER1 or DROSHA does not inhibit the angiogenic capacity of HUVEC. Further studies are therefore needed to elucidate the influence of these enzymes in the context of human endothelial cell-related angiogenesis.

2022-02-17 | PXD027923 | Pride

Proteomic analysis revealed the important role of vimentin in human cervical carcinoma HeLa cells treated with gambogic acid

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2018-10-24 | PXD002985 | Pride

Loss of apelin blocks the emergence of sprouting angiogenesis in experimental tumors

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2023-04-06 | E-MTAB-11663 | biostudies-arrayexpress

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2020-03-19 | PXD017518 | Pride

Activation of Epidermal Growth Factor Receptor Pathway in Slow-Flow Vascular Malformations

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2018-05-23 | PXD008591 | Pride

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