Evidence for critical role of Tie2/Ang1 interaction in metastatic oral cancer

Kawaguchi, Daisuke; Kasamatsu, Atsushi; Nakashima, Daisuke; Miyamoto, Isao; Kimura, Yasushi; Endo‐Sakamoto, Yosuke; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

doi:10.3892/ol.2018.8212

Cited by 7 publications

(6 citation statements)

References 51 publications

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“…37 Experimental study recently demonstrated that an in-vitro treatment with angiopoietin-1 for Tie2-overexpressed oral squamous cell carcinoma cells enhances the cell-cell and cellextracellular matrix adhesive activities of cancer cells. 38 This nding indicates that angiopoietin-1 directly up-regulates the functional activity of Tie2. In our study, the angiopoietin-1 plasma level was decreased after surgical resection, which may subsequently suppress the tyrosine phosphorylation level of Tie2 in erythrocyte membrane.…”

Section: Discussionmentioning

confidence: 87%

Stage-dependent angiopoietin-Tie2 and nitric oxide signaling of erythrocytes in response to surgical trauma in head and neck cancer

Chu

Tai

et al. 2020

Preprint

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Background: Angiopoietin-Tie2 and nitric oxide pathway is crucial in tumor angiogenesis and closely correlates with tumor development, growth, and metastasis. This study aimed to investigate the angiopoietin-Tie2 and nitric oxide signaling of erythrocyte membrane in response to surgical trauma in head and neck cancer.Methods: We prospectively enrolled the patients with histology-proven head and neck squamous cell carcinoma undergoing surgical resection of primary tumors at the medical center between August and November 2019. We measured the preoperative and postoperative levels of angiopoietin-1, angiopoietin-2 in plasma using enzyme-linked immunosorbent assays, nitric oxide in plasma using nitrate/nitrite colorimetric assays, and Tie2 phosphorylation in erythrocyte membrane using Western blotting. Results: The plasma angiopoietin-1 was down-regulated from median 971.3 pg/mL (interquartile range [IQR]: 532.1 – 1569.3) to 417.9 (IQR: 270.5 – 597.3) after tumor resection (p=0.0020). Conversely, the plasma angiopoietin-2 was enhanced from 1173.6 pg/mL (IQR: 977.7 – 1450.2) to 2353.7 (IQR: 1352.4 – 2954.3) after surgery (p=0.0021), with a concomitant increase in plasma nitric oxide level from 7.73 μM (IQR: 5.39 – 10.06) to 10.50 (IQR: 7.65 – 14.18) after surgical resection (p=0.0093). Subgroup analyses further showed the angiopoietin-Tie2 and nitric oxide signaling was significant only in stage III and IV cancer.Conclusions: The dynamic change of angiopoietin-Tie2 signaling in erythrocyte membrane along with the enhanced nitric oxide in plasma after tumor resection suggests erythrocytes play a significant role in modulating surgery-induced angiogenesis, which may provide a novel marker for cancer surveillance and control.

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Section: Discussionmentioning

confidence: 87%

Stage-dependent angiopoietin-Tie2 and nitric oxide signaling of erythrocytes in response to surgical trauma in head and neck cancer

Chu

Tai

et al. 2020

Preprint

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“…Tie2 is a receptor tyrosine kinase expressed principally on vascular endothelium and interacts with its ligand angiopoietin-1 and angiopoietin-2 in regulating vessel branching and maintaining endothelial homeostasis [ 36 ]. Experimental study recently demonstrated that an in vitro treatment with angiopoietin-1 for Tie2-overexpressed oral squamous cell carcinoma cells enhances the cell-cell and cell-extracellular matrix adhesive activities of cancer cells [ 37 ]. This finding indicates that angiopoietin-1 directly upregulates the functional activity of Tie2.…”

Section: Discussionmentioning

confidence: 99%

Stage-dependent angiopoietin-Tie2 and nitric oxide signaling of erythrocytes in response to surgical trauma in head and neck cancer

Chu

Tai

et al. 2020

World J Surg Onc

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Background Angiopoietin-Tie2 and nitric oxide pathway is crucial in tumor angiogenesis and closely correlates with tumor development, growth, and metastasis. This study aimed to investigate the angiopoietin-Tie2 and nitric oxide signaling of the erythrocyte membrane in response to surgical trauma in head and neck cancer. Methods We prospectively enrolled the patients with histology-proven head and neck squamous cell carcinoma undergoing surgical resection of primary tumors at the medical center between August and November 2019. We measured the preoperative and postoperative levels of angiopoietin-1, angiopoietin-2 in plasma using enzyme-linked immunosorbent assays, nitric oxide in plasma using nitrate/nitrite colorimetric assays, and Tie2 phosphorylation in erythrocyte membrane using Western blotting. Results The plasma angiopoietin-1 was downregulated from the median 971.3 pg/mL (interquartile range [IQR] 532.1–1569.3) to 417.9 (IQR 270.5–597.3) after tumor resection ( p = 0.0020). Conversely, the plasma angiopoietin-2 was enhanced from 1173.6 pg/mL (IQR 977.7–1450.2) to 2353.7 (IQR 1352.4–2954.3) after surgery ( p = 0.0021), with a concomitant increase in plasma nitric oxide level from 7.73 μM (IQR 5.39–10.06) to 10.50 (IQR 7.65–14.18) after surgical resection ( p = 0.0093). Subgroup analyses further showed the angiopoietin-Tie2 and nitric oxide signaling was significant only in stage III and IV cancer. Conclusions The dynamic change of angiopoietin-Tie2 signaling in the erythrocyte membrane along with the enhanced nitric oxide in plasma after tumor resection suggests erythrocytes play a significant role in modulating surgery-induced angiogenesis, which may provide a novel marker for cancer surveillance and control.

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“…Having identified a link between Ang1 and ARP2/3, we further evaluated the signaling pathway involved in Ang1-dependent ARP2/3 expression. Ang1 is known as a Tie2 agonist, which promotes phosphorylation of Tie2 to activate its downstream pathways [27,28]. Tie2 was initially found to be overexpressed in tumour vessels, while recent studies reported Tie2 expression in cancer cells [17,29].…”

Section: Ang1 Regulates Arp2/3 Expression Through Tie2-pi3k/akt Pathwaymentioning

confidence: 99%

Angiopoietin-1 Upregulates Cancer Cell Motility in Colorectal Cancer Liver Metastases through Actin-Related Protein 2/3

Rada

Kapelanski-Lamoureux

Tsamchoe

et al. 2022

Cancers

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Resistance to anti-angiogenic therapy is a major challenge in the treatment of colorectal cancer liver metastases (CRCLMs). Vessel co-option has been identified as a key contributor to anti-angiogenic therapy resistance in CRCLMs. Recently, we identified a positive correlation between the expression of Angiopoietin1 (Ang1) in the liver and the development of vessel co-opting CRCLM lesions in vivo. However, the mechanisms underlying its stimulation of vessel co-option are unclear. Herein, we demonstrated Ang1 as a positive regulator of actin-related protein 2/3 (ARP2/3) expression in cancer cells, in vitro and in vivo, which is known to be essential for the formation of vessel co-option in CRCLM. Significantly, Ang1-dependent ARP2/3 expression was impaired in the cancer cells upon Tie2 or PI3K/AKT inhibition in vitro. Taken together, our results suggest novel mechanisms by which Ang1 confers the development of vessel co-option in CRCLM, which, targeting this pathway, may serve as promising therapeutic targets to overcome the development of vessel co-option in CRCLM.

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Evidence for critical role of Tie2/Ang1 interaction in metastatic oral cancer

Cited by 7 publications

References 51 publications

Stage-dependent angiopoietin-Tie2 and nitric oxide signaling of erythrocytes in response to surgical trauma in head and neck cancer

Stage-dependent angiopoietin-Tie2 and nitric oxide signaling of erythrocytes in response to surgical trauma in head and neck cancer

Stage-dependent angiopoietin-Tie2 and nitric oxide signaling of erythrocytes in response to surgical trauma in head and neck cancer

Angiopoietin-1 Upregulates Cancer Cell Motility in Colorectal Cancer Liver Metastases through Actin-Related Protein 2/3

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