Integration of pro- and anti-angiogenic signals by endothelial cells

Kazerounian, Shiva; Lawler, Jack

doi:10.1007/s12079-017-0433-3

Cited by 82 publications

(54 citation statements)

References 91 publications

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“…Angiogenesis is a tightly balanced mechanism regulated by both pro-angiogenic and anti-angiogenic factors (13). In malignant tumors, this balance is shifted toward a pro-angiogenic milieu to maintain sustainable angiogenic processes (14).…”

Section: Angiogenesis: Regulationmentioning

confidence: 99%

Resistance Mechanisms to Anti-angiogenic Therapies in Cancer

et al. 2020

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Section: Angiogenesis: Regulationmentioning

confidence: 99%

Resistance Mechanisms to Anti-angiogenic Therapies in Cancer

et al. 2020

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“…VEGF is one of the most prominent pro-angiogenic factors 14 . HUVEC are known to secrete VEGF into culture medium and uptake it in an autocrine/paracrine manner 15 .…”

Section: Bm-mnc Promote Vegf Uptake Into Huvec Through Gap Junction Mmentioning

confidence: 99%

Bone Marrow Mononuclear Cells Activate Angiogenesis via Gap Junction–Mediated Cell-Cell Interaction

Kikuchi-Taura

Okinaka

Takeuchi

et al. 2020

Stroke

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Background and Purpose— Bone marrow mononuclear cells (BM-MNCs) are a rich source of hematopoietic stem cells and have been widely used in experimental therapies for patients with ischemic diseases. Activation of angiogenesis is believed to be one of major BM-MNC mode of actions, but the essential mechanism by which BM-MNCs activate angiogenesis have hitherto been elusive. The objective of this study is to reveal the mechanism how BM-MNCs activate angiogenesis. Methods— We have evaluated the effect of direct cell-cell interaction between BM-MNC and endothelial cell on uptake of VEGF (vascular endothelial growth factor) into endothelial cells in vitro. Cerebral ischemia model was used to evaluate the effects of direct cell-cell interaction with transplanted BM-MNC on endothelial cell at ischemic tissue. Results— The uptake of VEGF into endothelial cells was increased by BM-MNC, while being inhibited by blockading the gap junction. Low-molecular-weight substance was transferred from BM-MNC into endothelial cells via gap junctions in vivo, followed by increased expression of hypoxia-inducible factor-1α and suppression of autophagy in endothelial cells. The concentration of glucose in BM-MNC cytoplasm was significantly higher than in endothelial cells, and transfer of glucose homologue from BM-MNC to endothelial cells was observed. Conclusions— Our findings demonstrated cell-cell interaction via gap junction is the prominent pathway for activation of angiogenesis at endothelial cells after ischemia and provided novel paradigm that energy source supply by stem cell to injured cell is one of the therapeutic mechanisms of cell-based therapy. Visual Overview— An online visual overview is available for this article.

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“…Conclusively, tumor endothelial cells are actively involved in immune cell exclusion and inhibition of lymphocyte activation, fostering an immunosuppressive intratumoral microenvironment that contributes to the tumor immune escape and severely impairs conventional cancer therapies ( 9 , 14 , 69 ). Hypothetically, tumors resistant to immune checkpoint blockade could become sensitive to such treatment again when the tumor endothelium specific alterations in leukocyte-endothelial adhesive interactions were normalized.…”

Section: Tumor Endothelium-mediated Regulation Of the Immune Responsementioning

confidence: 99%

The Tumor Vascular Endothelium as Decision Maker in Cancer Therapy

2018

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Genetic and pathophysiologic criteria prearrange the uncontrolled growth of neoplastic cells that in turn initiates new vessel formation, which is prerequisite for further tumor growth and progression. This first endothelial lining is patchy, disordered in structure and thus, angiogenic tumor vessels were proven to be functionally inferior. As a result, tumors were characterized by areas with an apparent oversupply in addition to areas with an undersupply of vessels, which complicates an efficient administration of intravenous drugs in cancer therapy and might even lower the response e.g. of radiotherapy (RT) because of the inefficient oxygen supply. In addition to the vascular dysfunction, tumor blood vessels contribute to the tumor escape from immunity by the lack of response to inflammatory activation (endothelial anergy) and by repression of leukocyte adhesion molecule expression. However, tumor vessels can remodel by the association with and integration of pericytes and smooth muscle cells which stabilize these immature vessels resulting in normalization of the vascular structures. This normalization of the tumor vascular bed could improve the efficiency of previously established therapeutic approaches, such as chemo- or radiotherapy by a more homogenous drug and oxygen distribution, and/or by overcoming endothelial anergy. This review highlights the current investigations that take advantage of a proper vascular function for improving cancer therapy with a special focus on the endothelial-immune system interplay.

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Integration of pro- and anti-angiogenic signals by endothelial cells

Cited by 82 publications

References 91 publications

Resistance Mechanisms to Anti-angiogenic Therapies in Cancer

Resistance Mechanisms to Anti-angiogenic Therapies in Cancer

Bone Marrow Mononuclear Cells Activate Angiogenesis via Gap Junction–Mediated Cell-Cell Interaction

The Tumor Vascular Endothelium as Decision Maker in Cancer Therapy

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