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Distinct role of autophagy on angiogenesis: highlights on the effect of autophagy in endothelial lineage and progenitor cells.

ABSTRACT: Autophagy plays a critical role in the dynamic growth of each cell through different conditions. It seems that this intracellular mechanism acts as a two-edged sword against the numerous cell insults. Previously, autophagy was described in the context of cell activity and behavior, but little knowledge exists related to the role of autophagy in endothelial cells, progenitors, and stem cells biology from different tissues. Angiogenic behavior of endothelial lineage and various stem cells are touted as an inevitable feature in the restoration of different damaged tissues and organs. This capacity was found to be dictated by autophagy signaling pathway. This review article highlights the fundamental role of cell autophagic response in endothelial cells function, stem cells dynamic, and differentiation rate. It seems that elucidation of the mechanisms related to pro- and/or anti-angiogenic potential of autophagy inside endothelial cells and stem cells could help us to modulate stem cell therapeutic feature post-transplantation.

SUBMITTER: Hassanpour M

PROVIDER: S-EPMC6225658 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Distinct role of autophagy on angiogenesis: highlights on the effect of autophagy in endothelial lineage and progenitor cells.

Hassanpour Mehdi M Rezabakhsh Aysa A Pezeshkian Masoud M Rahbarghazi Reza R Nouri Mohammad M

Stem cell research & therapy 20181108 1

Autophagy plays a critical role in the dynamic growth of each cell through different conditions. It seems that this intracellular mechanism acts as a two-edged sword against the numerous cell insults. Previously, autophagy was described in the context of cell activity and behavior, but little knowledge exists related to the role of autophagy in endothelial cells, progenitors, and stem cells biology from different tissues. Angiogenic behavior of endothelial lineage and various stem cells are tout ...[more]

PMID: 30409213

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Project description:BACKGROUND:Controlling vascular growth is a challenging aim for the inhibition of tumor growth and metastasis. The amoeboid and mesenchymal types of invasiveness are two modes of migration interchangeable in cancer cells: the Rac-dependent mesenchymal migration requires the activity of proteases; the Rho-ROCK-dependent amoeboid motility is protease-independent and has never been described in endothelial cells. METHODS:A cocktail of physiologic inhibitors (Ph-C) of serine-proteases, metallo-proteases and cysteine-proteases, mimicking the physiological environment that cells encounter during their migration within the angiogenesis sites was used to induce amoeboid style migration of Endothelial colony forming cells (ECFCs) and mature endothelial cells (ECs). To evaluate the mesenchymal-ameboid transition RhoA and Rac1 activation assays were performed along with immunofluorescence analysis of proteins involved in cytoskeleton organization. Cell invasion was studied in Boyden chambers and Matrigel plug assay for the in vivo angiogenesis. RESULTS:In the present study we showed in both ECFCs and ECs, a decrease of activated Rac1 and an increase of activated RhoA upon shifting of cells to the amoeboid conditions. In presence of Ph-C inhibitors both cell lines acquired a round morphology and Matrigel invasion was greatly enhanced with respect to that observed in the absence of protease inhibition. We also observed that the urokinase-plasminogen-activator (uPAR) receptor silencing and uPAR-integrin uncoupling with the M25 peptide abolished both mesenchymal and amoeboid angiogenesis of ECFCs and ECs in vitro and in vivo, indicating a role of the uPAR-integrin-actin axis in the regulation of amoeboid angiogenesis. Furthermore, under amoeboid conditions endothelial cells seem to be indifferent to VEGF stimulation, which induces an amoeboid signaling pattern also in mesenchymal conditions. CONCLUSION:Here we first provide a data set disclosing that endothelial cells can move and differentiate into vascular structures in vitro and in vivo also in the absence of proteases activity, performing a new type of neovascularization: the "amoeboid angiogenesis". uPAR is indispensable for ECs and ECFCs to perform an efficient amoeboid angiogenesis. Therefore, uPAR silencing or the block of its integrin-interaction, together with standard treatment against VEGF, could be a possible solution for angiogenesis inhibition.

Dataset Information

Distinct role of autophagy on angiogenesis: highlights on the effect of autophagy in endothelial lineage and progenitor cells.

Publications

Distinct role of autophagy on angiogenesis: highlights on the effect of autophagy in endothelial lineage and progenitor cells.

Similar Datasets

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