Angiopoietins Modulate Survival, Migration, and the Components of the Ang-Tie2 Pathway of Chronic Lymphocytic Leukaemia (CLL) Cells In Vitro

Palma, Luis Mario Aguirre; Flamme, Hanna; Gerke, Iris; Kreuzer, Karl‐Anton

doi:10.1007/s12307-016-0180-7

Cited by 15 publications

(6 citation statements)

References 50 publications

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“…In this study, we show ANGPT2 was significantly elevated in NI patients compared to healthy controls and, although it was higher in NP patient plasma compared to controls, this did not reach significance. It is of interest that ANGPT2 is a key player in the ANGPT2-Tie2 pro-angiogenic pathway and also in the metabolic fitness of a number of cells 55 . Since we found that both angiogenesis and mitochondrial activity were higher in NI ECFCs compared to the NP, these data correlated with the elevated levels of ANGPT2 that were detected in the NI vs NP cells.…”

Section: Discussionmentioning

confidence: 99%

Diabetic endothelial colony forming cells have the potential for restoration with glycomimetics

Langford-Smith

Hasan

Weston

et al. 2019

Sci Rep

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Endothelial colony forming progenitor cell (ECFC) function is compromised in diabetes, leading to poor vascular endothelial repair, which contributes to impaired diabetic foot ulcer healing. We have generated novel glycomimetic drugs with protective effects against endothelial dysfunction. We investigated the effect of glycomimetic C3 on the functional capacity of diabetic ECFCs. ECFCs were isolated from healthy controls and patients with diabetes with neuroischaemic (NI) or neuropathic (NP) foot ulcers. Functionally, diabetic ECFCs demonstrated delayed colony formation (p < 0.02), differential proliferative capacity (p < 0.001) and reduced NO bioavailability (NI ECFCs; p < 0.05). Chemokinetic migration and angiogenesis were also reduced in diabetic ECFCs (p < 0.01 and p < 0.001), and defects in wound closure and tube formation were apparent in NP ECFCs (p < 0.01). Differential patterns in mitochondrial activity were pronounced, with raised activity in NI and depressed activity in NP cells (p < 0.05). The application of glycomimetic improved scratch wound closure in vitro in patient ECFCs (p < 0.01), most significantly in NI cells (p < 0.001), where tube formation (p < 0.05) was also improved. We demonstrate restoration of the deficits in NI cells but not NP cells, using a novel glycomimetic agent, which may be advantageous for therapeutic cell transplantation or as a localised treatment for NI but not NP patients.

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Section: Discussionmentioning

confidence: 99%

Diabetic endothelial colony forming cells have the potential for restoration with glycomimetics

Langford-Smith

Hasan

Weston

et al. 2019

Sci Rep

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“…This is not altogether surprising considering the stimulation of angiogenesis is probably the key role of TEM [ 3 , 5 , 9 ]. The importance of the process has been described not only in the development of solid tumors but also in the pathomechanism of lymphoproliferative tumors, including CLL [ 32 , 33 , 34 ]. CLL patients demonstrate increased vascularization density of lymph nodes [ 32 ] and bone marrow [ 33 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of Tie2-Expressing Monocytes in Chronic Lymphocytic Leukemia Patients

Woś

Chocholska

Kowalska

et al. 2021

Cancers

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Tie2-expressing monocytes (TEMs) are associated with tumor progression and metastasis. This unique subset of monocytes has been identified as a potential prognostic marker in several solid tumors. However, TEMs remain poorly characterized in hematological cancers, including chronic lymphocytic leukemia (CLL). This study analyzed, for the first time, the clinical significance of TEM population in CLL patients. Flow cytometry analysis of TEMs (defined as CD14+CD16+Tie2+ cells) was performed at the time of diagnosis on peripheral blood mononuclear cells from 104 untreated CLL patients. Our results revealed an expansion of circulating TEM in CLL patients. These monocytes express high levels of VEGF and suppressive IL-10. A high percentage of TEM was associated closely with unfavorable prognostic markers (ZAP-70, CD38, 17p and 11q deletion, and IGHV mutational status). Moreover, increased percentages of circulating TEMs were significantly higher in patients not responding to the first-line therapy as compared to responding patients, suggesting its potential predictive value. High TEM percentage was also correlated with shorter overall survival (OS) and shorter time to treatment (TTT). Importantly, based on multivariate Cox regression analysis, TEM percentage was an independent predictor for TTT. Thus, we can suggest the adverse role of TEMs in CLL.

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“…Nowadays, it is widely recognized that angiogenesis promotes the proliferation of malignant cells in CLL [43]; however, the molecular mechanisms of this process are still poorly understood. Tumor substrate cells in CLL produce a large number of angiogenic factors, thus stimulating angiogenesis [44]. Excessive expression of these factors leads to microenvironmental dysfunction, supports proliferation of malignant B-lymphocytes and increases their resistance to apoptosis.…”

Section: Relationship Between Pathological Angiogenesis and Vegf Levelmentioning

confidence: 99%

“…Some publications describe that natural killer (NK) cells produce various proangiogenic factors in humans and mice [57], such as VEGF and PIGF, which can significantly accelerate tumor growth [58]. In patients suffering from CLL, it was shown that tumor clone cells produce angiogenic factors, including VEGF, stimulating cell proliferation [43,44].…”

Section: Relationship Between Pathological Angiogenesis and Vegf Levelmentioning

confidence: 99%

Endothelial dysfunction in patients with lymphoproliferative disorders and its changes in the course of polychemotherapy

et al. 2020

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The article is dedicated to contemporary views on the change of endothelial function in the patients with lymphoproliferative disorders prior to, and in the process of, chemotherapeutic treatment. Considering that possibilities of standard examination do not always help identifying subclinical endothelial dysfunction, it is necessary to use specific methods, in particular, to determine the levels of endothelin-1 and vascular endothelial growth factor to monitor endothelial function. The objective of this review is to identify problems and prospects for recognizing early subclinical changes of endothelial function in the patients with lymphoproliferative disorders before and after chemotherapy. Assessing presence and severity of endothelial dysfunction may be useful for determining subclinical stages of cardiovascular damage, stratifying the risk of the patients with confirmed cardiovascular disease, and reducing the likelihood of cardio- and endotheliotoxic effects in patients long after chemotherapy. That is why early detection and immediate therapy of cardiovascular toxicity is currently the most important task in the patients with lymphoproliferative disorders, receiving chemotherapy.

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Angiopoietins Modulate Survival, Migration, and the Components of the Ang-Tie2 Pathway of Chronic Lymphocytic Leukaemia (CLL) Cells In Vitro

Abstract: In actuality, chronic lymphocytic leukaemia (CLL) remains an incurable haematopoietic malignancy of high prevalence amongst elderly populations in the West.

Cited by 15 publications

References 50 publications

Diabetic endothelial colony forming cells have the potential for restoration with glycomimetics

Diabetic endothelial colony forming cells have the potential for restoration with glycomimetics

Prognostic Value of Tie2-Expressing Monocytes in Chronic Lymphocytic Leukemia Patients

Endothelial dysfunction in patients with lymphoproliferative disorders and its changes in the course of polychemotherapy

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