HMEC-1 adopt the mixed amoeboid-mesenchymal migration type during EndMT

Kryczka, Jakub; Przygodzka, Patrycja; Bogusz, Helena; Boncela, Joanna

doi:10.1016/j.ejcb.2017.04.002

Cited by 15 publications

(22 citation statements)

References 97 publications

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“…However, a possible amoeboid movement of ECFCs has been suggested only on the basis of cell morphology [ 1 , 11 , 29 , 30 ]. A recent paper [ 31 ] has described an amoeboid phase of endothelial cells engaged in the endothelial to mesenchymal transition in the frame of Systemic Sclerosis-associated fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Mature and progenitor endothelial cells perform angiogenesis also under protease inhibition: the amoeboid angiogenesis

Chillà¹,

Margheri²,

Biagioni³

et al. 2018

J Exp Clin Cancer Res

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BackgroundControlling 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.MethodsA 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.ResultsIn 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.ConclusionHere 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.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0742-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Mature and progenitor endothelial cells perform angiogenesis also under protease inhibition: the amoeboid angiogenesis

Chillà¹,

Margheri²,

Biagioni³

et al. 2018

J Exp Clin Cancer Res

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“…Cell migration is a very composed process, regulated by many often, ostensibly not migratory related signalling pathways, that allow cells to dynamically adjust to microenvironment changes inflicted by a variety of factors (e.g., growth factors, cytokines, mediators of inflammation, physical/mechanical irritation, etc.) [ 126 ]. Thus, it has become a cutting-edge field in cancer research.…”

Section: Non-canonical Activity Of Abc Transporters In Cell Migratmentioning

confidence: 99%

“…The ameboid migration of cells is characterized by a three times higher velocity (0.6–0.8 µm/min) than the mesenchymal (0.2 µm/min) type. Moreover, it is strongly dependent on Rho/ROCK (Rho-associated kinase) activity, phosphorylation of myosin II, and it is independent of extracellular matrix (ECM) degradation and cell adhesion [ 126 ]. On the other hand, mesenchymal type migration exhibits elongated cell morphology with long protrusions.…”

Section: Non-canonical Activity Of Abc Transporters In Cell Migratmentioning

confidence: 99%

“…On the other hand, mesenchymal type migration exhibits elongated cell morphology with long protrusions. It is strongly dependent on Rac kinase activity, proteolytic degradation of ECM components and adhesion via integrins [ 126 ]. Both small GTPases Rho and Rac belong to the Ras family; however, they exert opposite effects.…”

Section: Non-canonical Activity Of Abc Transporters In Cell Migratmentioning

confidence: 99%

“…Proteins that act in the antiamoeboid mode activate Rac signalling [ 129 ]. However, intermediate model between ameboid and mesenchymal has recently been proposed, suggesting that cells may shift between the types of migration according to many factors, such as changes in microenvironment plasticity, loss of close cell-cell connections (tight junctions), availability of the vascular endothelial growth factor (VEGF) isoforms as observed for fibrosarcoma [ 130 ] or chemokines and growth factors released by inflammatory cells as reported for microvascular endothelial cells [ 126 , 131 ]. Migration type shift enables effective migration in changing environments (changes in ECM substrates, breaching anatomical boundaries, etc.)…”

Section: Non-canonical Activity Of Abc Transporters In Cell Migratmentioning

confidence: 99%

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Cell Migration Related to MDR—Another Impediment to Effective Chemotherapy?

Kryczka

Boncela

2018

Molecules

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Multidrug resistance, mediated by members of the ATP-binding cassette (ABC) proteins superfamily, has become one of the biggest obstacles in conquering tumour progression. If the chemotherapy outcome is considered successful, when the primary tumour volume is decreased or completely abolished, modulation of ABC proteins activity is one of the best methods to overcome drug resistance. However, if a positive outcome is represented by no metastasis or, at least, elongation of remission-free time, then the positive effect of ABC proteins inhibition should be compared with the several side effects it causes, which may inflict cancer progression and decrease overall patient health. Clinical trials conducted thus far have shown that the tested ABC modulators add limited or no benefits to cancer patients, as some of them are merely toxic and others induce unwanted drug–drug interactions. Moreover, the inhibition of certain ABC members has been recently indicated as potentially responsible for increased fibroblasts migration. A better understanding of the complex role of ABC proteins in relation to cancer progression may offer novel strategies in cancer therapy.

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