scholarly journals VE-PTP participates in vasculogenic mimicry by preventing autophagic degradation of VE-cadherin

2019 ◽  
Author(s):  
Daniel Delgado-Bellido ◽  
Concepción Bueno-Galera ◽  
Angel Garcia-Diaz ◽  
F. Javier Oliver

AbstractAberrant extra-vascular expression of VE-cadherin has been observed in metastasis associated with Vasculogenic Mimicry (VM); we have recently shown that in VM prone (VM+) tumor cells VE-cadherin is mainly in the form of pVE-cadherin in Y658 allowing an increased plasticity that potentiates VM development. As excessive VE-cadherin phosphorylation is regulated by the phosphatase VEPTP in endothelial cells in the current study we analysed its role in this aberrant phenotype in malignant tumor cells. We show that human malignant melanoma cells VM+, also express VE-PTP although at lower levels than endothelial cells. The complex VE-PTP/VE-Cadherin/p120-catenin act as a safeguard to prevent VE-cadherin degradation by autophagy. Indeed, silencing of VE-PTP results in complete degradation of VE-cadherin with the features of autophagy and increases the global p120 tyrosine phosphorylation status. In summary, we show that VE-PTP is involved in VM formation and disruption of VE-PTP/VE-Cadherin/p120 complex results in enhanced autophagy in aggressive VM+ cells.

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1539 ◽  
Author(s):  
Peter Ping Lin

Hematogenous and lymphogenous cancer metastases are significantly impacted by tumor neovascularization, which predominantly consists of blood vessel-relevant angiogenesis, vasculogenesis, vasculogenic mimicry, and lymphatic vessel-related lymphangiogenesis. Among the endothelial cells that make up the lining of tumor vasculature, a majority of them are tumor-derived endothelial cells (TECs), exhibiting cytogenetic abnormalities of aneuploid chromosomes. Aneuploid TECs are generated from “cancerization of stromal endothelial cells” and “endothelialization of carcinoma cells” in the hypoxic tumor microenvironment. Both processes crucially engage the hypoxia-triggered epithelial-to-mesenchymal transition (EMT) and endothelial-to-mesenchymal transition (EndoMT). Compared to the cancerization process, endothelialization of cancer cells, which comprises the fusion of tumor cells with endothelial cells and transdifferentiation of cancer cells into TECs, is the dominant pathway. Tumor-derived endothelial cells, possessing the dual properties of cancerous malignancy and endothelial vascularization ability, are thus the endothelialized cancer cells. Circulating tumor-derived endothelial cells (CTECs) are TECs shed into the peripheral circulation. Aneuploid CD31+ CTECs, together with their counterpart CD31- circulating tumor cells (CTCs), constitute a unique pair of cellular circulating tumor biomarkers. This review discusses a proposed cascaded framework that focuses on the origins of TECs and CTECs in the hypoxic tumor microenvironment and their clinical implications for tumorigenesis, neovascularization, disease progression, and cancer metastasis. Aneuploid CTECs, harboring hybridized properties of malignancy, vascularization and motility, may serve as a unique target for developing a novel metastasis blockade cancer therapy.


1976 ◽  
Vol 277 (1) ◽  
pp. 355-366 ◽  
Author(s):  
Henry R. Shibata ◽  
L. Martin Jerry ◽  
Martin G. Lewis ◽  
Peter W. A. Mansell ◽  
Alena Capek ◽  
...  

1984 ◽  
Vol 294 (2) ◽  
pp. 381-384 ◽  
Author(s):  
Toshiaki Isobe ◽  
Kayoko Ichimori ◽  
Takashi Nakajima ◽  
Tsuneo Okuyama

2017 ◽  
Vol 63 (6) ◽  
pp. 894-899
Author(s):  
Viktor Novik ◽  
A. Nefedova ◽  
Ye. Yakubo ◽  
O. Ivanov ◽  
Yekaterina Shalina ◽  
...  

Cytological examination of smears from the sediment after centrifugation of pleural fluids was performed in 479 patients who underwent examination and treatment at our institution in 2014-2016. In 249 (52%) patients tumor cells were not detected in smears, in 230 (48%) observations a suspicion (28 observations) or a confident conclusion (202 observations) on the presence of malignant tumor cells in the exudates was cytologically expressed. In 38 cases immunocytochemical studies was additionally performed. In two observations a false-negative conclusion about the absence of tumor cells in smears was expressed. The sensitivity of the cytological study in the diagnosis of malignant pleuritis was 99.0%. Affirmative cytological conclusions on the presence of malignant pleuritis were given in 87.0% of observations, suspicious cytological responses - in 12.0% of cases. Immunocytochemical studies significantly expanded the possibilities of cytological research and were of great importance in the diagnosis of metastases of tumors of unknown primary localization.


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