scholarly journals Phosphorylation of pericyte FAK-Y861 affects tumour cell apoptosis and tumour blood vessel regression

2020 ◽  
Author(s):  
Delphine M. Lees ◽  
Louise E. Reynolds ◽  
Ana Rita Pedrosa ◽  
Marina Roy-Luzarraga ◽  
Kairbaan M. Hodivala-Dilke
Keyword(s):  
Blood Vessel ◽  
Tumour Growth ◽  
Vascular Endothelial Cell ◽  
Growth Control ◽  
Vessel Density ◽  
Blood Vessel Density ◽  
Tumour Vessel ◽  
Vessel Regression ◽  
Tumour Blood

AbstractFocal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is overexpressed in many cancer types and in vivo studies have shown that vascular endothelial cell FAK expression and FAK-phosphorylation at tyrosine (Y) 397, and subsequently FAK-Y861, are important in tumour angiogenesis. Pericytes also play a vital role in regulating tumour blood vessel stabilisation, but the involvement of pericyte FAK-Y397 and FAK-Y861 phosphorylation in tumour blood vessels is unknown. Using PdgfrβCre+;FAKWT/WT, PdgfrβCre+;FAKY397F/Y397F and PdgfrβCre+;FAKY861F/Y861F mice, our data demonstrate that tumour growth, tumour blood vessel density, blood vessel perfusion and pericyte coverage were affected only in late stage tumours in PdgfrβCre+;FAKY861F/Y861F but not PdgfrβCre+;FAKY397F/Y397F mice. Further examination indicates a dual role for pericyte FAK-Y861 phosphorylation in the regulation of tumour vessel regression and also in the control of a pericyte derived ‘pericrine’ signals that influence apoptosis in cancer cells. Overall this study identifies the role of pericyte FAK-Y861 in the regulation of tumour vessel regression and tumour growth control and that non-phosphorylatable FAK-Y861F in pericytes reduces tumour growth and blood vessel density.

scholarly journals Phosphorylation of pericyte FAK-Y861 affects tumour cell apoptosis and tumour blood vessel regression

Angiogenesis ◽  
2021 ◽  
Author(s):  
Delphine M. Lees ◽  
Louise E. Reynolds ◽  
Ana Rita Pedrosa ◽  
Marina Roy-Luzarraga ◽  
Kairbaan M. Hodivala-Dilke
Keyword(s):  
Blood Vessel ◽  
Tumour Growth ◽  
Vascular Endothelial Cell ◽  
Vessel Density ◽  
In Vivo Studies ◽  
Blood Vessel Density ◽  
Tumour Vessel ◽  
Vessel Regression ◽  
Tumour Blood

AbstractFocal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is overexpressed in many cancer types and in vivo studies have shown that vascular endothelial cell FAK expression and FAK-phosphorylation at tyrosine (Y) 397, and subsequently FAK-Y861, are important in tumour angiogenesis. Pericytes also play a vital role in regulating tumour blood vessel stabilisation, but the specific involvement of pericyte FAK-Y397 and FAK-Y861 phosphorylation in tumour blood vessels is unknown. Using PdgfrβCre + ;FAKWT/WT, PdgfrβCre + ;FAKY397F/Y397F and PdgfrβCre + ;FAKY861F/Y861F mice, our data demonstrate that tumour growth, tumour blood vessel density, blood vessel perfusion and pericyte coverage were affected only in late stage tumours in PdgfrβCre + ;FAKY861F/Y861F but not PdgfrβCre + ;FAKY397F/Y397F mice. Further examination indicates a dual role for pericyte FAK-Y861 phosphorylation in the regulation of tumour vessel regression and also in the control of pericyte derived signals that influence apoptosis in cancer cells. Overall this study identifies the role of pericyte FAK-Y861 in the regulation of tumour vessel regression and tumour growth control and that non-phosphorylatable FAK-Y861F in pericytes reduces tumour growth and blood vessel density.

scholarly journals Immunohistochemistry Evaluation of the Effect in Vivo of Tumor Necrosis Factor (TNF)-α on Blood Vessel Density in Murine Fibrosarcoma

Sarcoma ◽  
2003 ◽  
Vol 7 (2) ◽  
pp. 57-61 ◽  
Author(s):  
Avi Eisenthal ◽  
Ignat Schwartz ◽  
Josephine Issakov ◽  
Yossef Klausner ◽  
Faina Misonzhnik ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Blood Vessel ◽  
Tumor Necrosis ◽  
Vessel Density ◽  
Blood Vessel Density ◽  
Tnf Α ◽  
Murine Fibrosarcoma ◽  
Necrosis Factor

scholarly journals In Vivo Tumor Vascular Imaging with Light Emitting Diode-Based Photoacoustic Imaging System

Sensors ◽  
2020 ◽  
Vol 20 (16) ◽  
pp. 4503 ◽  
Author(s):  
Marvin Xavierselvan ◽  
Mithun Kuniyil Ajith Singh ◽  
Srivalleesha Mallidi
Keyword(s):  
Cancer Research ◽  
Blood Vessel ◽  
Imaging System ◽  
Light Emitting Diode ◽  
Tumor Vasculature ◽  
Vessel Density ◽  
Excitation Wavelength ◽  
Light Emitting ◽  
Blood Vessel Density

Photoacoustic (PA) imaging has shown tremendous promise for imaging tumor vasculature and its function at deeper penetration depths without the use of exogenous contrast agents. Traditional PA imaging systems employ expensive and bulky class IV lasers with low pulse repetition rate, due to which its availability for preclinical cancer research is hampered. In this study, we evaluated the capability of a Light-Emitting Diode (LED)-based PA and ultrasound (US) imaging system for monitoring heterogeneous microvasculature in tumors (up to 10 mm in depth) and quantitatively compared the PA images with gold standard histology images. We used a combination of a 7 MHz linear array US transducer and 850 nm excitation wavelength LED arrays to image blood vessels in a subcutaneous tumor model. After imaging, the tumors were sectioned and stained for endothelial cells to correlate with PA images across similar cross-sections. Analysis of 30 regions of interest in tumors from different mice showed a statistically significant R-value of 0.84 where the areas with high blood vessel density had high PA response while low blood vessel density regions had low PA response. Our results confirm that LED-based PA and US imaging can provide 2D and 3D images of tumor vasculature and the potential it has as a valuable tool for preclinical cancer research.

scholarly journals Increased Skin Inflammation and Blood Vessel Density in Human and Experimental Diabetes

2013 ◽  
Vol 12 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Ana Tellechea ◽  
Antonios Kafanas ◽  
Ermelindo C. Leal ◽  
Francesco Tecilazich ◽  
Sarada Kuchibhotla ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Blood Vessels ◽  
Experimental Diabetes ◽  
Human Subjects ◽  
Inflammatory Cells ◽  
Skin Inflammation ◽  
Vessel Density ◽  
Impaired Wound Healing ◽  
Blood Vessel Density ◽  
Skin Blood Vessels

Systemic inflammation is associated with impaired wound healing in diabetes mellitus (DM) patients. Using immunohistochemistry techniques, the authors investigated changes in skin inflammation and skin blood vessels in human and experimental diabetes. Comparing to the non-DM human subjects, the total number of inflammatory cells per biopsy and the number of inflammatory cells around blood vessels, a strong indication of inflammation, were higher in DM subjects irrespective of their risk for developing diabetic foot ulcer. Inflammatory cell infiltration was robustly increased in all DM animal models compared with their non-DM controls. The number and density of blood vessels and CD31 positive proliferating endothelial cells around preexisting skin vessels was also higher in the DM patients. However, there were no differences in the skin blood flow between the non-DM and DM subjects. The number of skin blood vessels was also increased in the DM animals; however, these differences were less obvious than the ones observed for inflammatory cells. We conclude that skin inflammation and skin blood vessel density is increased in diabetic human subjects and in rodent and rabbit models of diabetes.

Prognostic value of blood vessel density in ischaemic stroke

The Lancet ◽  
1993 ◽  
Vol 342 (8873) ◽  
pp. 742 ◽  
Author(s):  
J. Krupinski ◽  
J. Kaluza ◽  
P. Kumar ◽  
M. Wang ◽  
S. Kumar
Keyword(s):  
Blood Vessel ◽  
Ischaemic Stroke ◽  
Prognostic Value ◽  
Vessel Density ◽  
Blood Vessel Density

scholarly journals Cancer therapeutic potential of combinatorial immuno- and vasomodulatory interventions

2015 ◽  
Vol 12 (112) ◽  
pp. 20150439 ◽  
Author(s):  
H. Hatzikirou ◽  
J. C. L. Alfonso ◽  
S. Mühle ◽  
C. Stern ◽  
S. Weiss ◽  
...  
Keyword(s):  
Tumour Growth ◽  
Effector Cell ◽  
Therapeutic Potential ◽  
Growth Control ◽  
Therapeutic Window ◽  
Effector Cells ◽  
Cell Recruitment ◽  
Tumour Control ◽  
Tumour Vasculature

Currently, most of the basic mechanisms governing tumour–immune system interactions, in combination with modulations of tumour-associated vasculature, are far from being completely understood. Here, we propose a mathematical model of vascularized tumour growth, where the main novelty is the modelling of the interplay between functional tumour vasculature and effector cell recruitment dynamics. Parameters are calibrated on the basis of different in vivo immunocompromised Rag1 −/− and wild-type (WT) BALB/c murine tumour growth experiments. The model analysis supports that tumour vasculature normalization can be a plausible and effective strategy to treat cancer when combined with appropriate immunostimulations. We find that improved levels of functional tumour vasculature, potentially mediated by normalization or stress alleviation strategies, can provide beneficial outcomes in terms of tumour burden reduction and growth control. Normalization of tumour blood vessels opens a therapeutic window of opportunity to augment the antitumour immune responses, as well as to reduce intratumoral immunosuppression and induced hypoxia due to vascular abnormalities. The potential success of normalizing tumour-associated vasculature closely depends on the effector cell recruitment dynamics and tumour sizes. Furthermore, an arbitrary increase in the initial effector cell concentration does not necessarily imply better tumour control. We evidence the existence of an optimal concentration range of effector cells for tumour shrinkage. Based on these findings, we suggest a theory-driven therapeutic proposal that optimally combines immuno- and vasomodulatory interventions.

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