α4β1 integrin associates with VEGFR2 in CLL cells and contributes to VEGF binding and intracellular signaling

Gutiérrez-González, Alejandra; Aguilera-Montilla, Noemí; Ugarte-Berzal, Estefanía; Bailón, Elvira; Cerro-Pardo, Isabel; Sánchez-Maroto, Clara; García-Campillo, Lara; García-Marco, José A.; García-Pardo, Ángeles

doi:10.1182/bloodadvances.2019000019

Cited by 9 publications

(12 citation statements)

References 24 publications

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“…However, the adsorbed VEGF-A 165 enhanced the adhesion of lymphocytic leukemia cells and B lymphocytes, mediated with the direct association of α 4 β 1 integrin with vascular endothelial growth factor receptor-2 (VEGFR-2). The adhesion of B lymphocytes to adsorbed VEGF-A 165 was optimal at a concentration of 8 µg/mL (0.4 µM) [ 15 ].…”

Section: Resultsmentioning

confidence: 99%

“…VEGF-A 165 has also been widely used for experimental work in vitro, e.g., creation of vascularized tissue-engineered constructs, intended for bone regeneration [ 12 ] or functionalization of a decellularized pericardial matrix, intended for cardiovascular tissue engineering, in order to promote its recellularization with endothelial and stem cells [ 13 ]. In this context, it is worth mentioning that VEGF-A 165 immobilized on cell cultivation substrates can also act as an extracellular adhesion molecule, binding to integrin adhesion receptors on cells [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Growth Factors VEGF-A165 and FGF-2 as Multifunctional Biomolecules Governing Cell Adhesion and Proliferation

Sedlář

Trávníčková

Matějka

et al. 2021

IJMS

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Vascular endothelial growth factor-A165 (VEGF-A165) and fibroblast growth factor-2 (FGF-2) are currently used for the functionalization of biomaterials designed for tissue engineering. We have developed a new simple method for heterologous expression and purification of VEGF-A165 and FGF-2 in the yeast expression system of Pichia pastoris. The biological activity of the growth factors was assessed in cultures of human and porcine adipose tissue-derived stem cells (ADSCs) and human umbilical vein endothelial cells (HUVECs). When added into the culture medium, VEGF-A165 stimulated proliferation only in HUVECs, while FGF-2 stimulated the proliferation of both cell types. A similar effect was achieved when the growth factors were pre-adsorbed to polystyrene wells. The effect of our recombinant growth factors was slightly lower than that of commercially available factors, which was attributed to the presence of some impurities. The stimulatory effect of the VEGF-A165 on cell adhesion was rather weak, especially in ADSCs. FGF-2 was a potent stimulator of the adhesion of ADSCs but had no to negative effect on the adhesion of HUVECs. In sum, FGF-2 and VEGF-A165 have diverse effects on the behavior of different cell types, which maybe utilized in tissue engineering.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Growth Factors VEGF-A165 and FGF-2 as Multifunctional Biomolecules Governing Cell Adhesion and Proliferation

Sedlář

Trávníčková

Matějka

et al. 2021

IJMS

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“…A putative functional role for NGAL in CLL has not yet been reported. Early studies showed enhanced serum levels of TNF-α, VEGF and proMMP-9 in patients with CLL [47][48][49], in correlation with their overexpression and release by CLL lymphocytes [49][50][51] and their implication in CLL cell survival [37,50,52,53]. NF-κB also regulates the transcription of these inflammatory molecules [54,55].…”

Section: Discussionmentioning

confidence: 99%

Relation of Neutrophil Gelatinase-Associated Lipocalin Overexpression to the Resistance to Apoptosis of Tumor B Cells in Chronic Lymphocytic Leukemia

Bauvois

Pramil

Jondreville

et al. 2020

Cancers

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The resistance to apoptosis of chronic lymphocytic leukemia (CLL) cells partly results from the deregulated production of survival signals from leukemic cells. Despite the development of new therapies in CLL, drug resistance and disease relapse still occur. Recently, neutrophil gelatinase-associated lipocalin (NGAL), a secreted glycoprotein, has been suggested to have a critical role in the biology of tumors. Thus, we investigated the relevance of NGAL in CLL pathogenesis, analyzed the expression of its cellular receptor (NGAL-R) on malignant B cells and tested whether CLL cells are resistant to apoptosis through an autocrine process involving NGAL and NGAL-R. We observed that NGAL concentrations were elevated in the serum of CLL patients at diagnosis. After treatment (and regardless of the therapeutic regimen), serum NGAL levels normalized in CLL patients in remission but not in relapsed patients. In parallel, NGAL and NGAL-R were upregulated in leukemic cells from untreated CLL patients when compared to normal peripheral blood mononuclear cells (PBMCs), and returned to basal levels in PBMCs from patients in remission. Cultured CLL cells released endogenous NGAL. Anti-NGAL-R antibodies enhanced NGAL-R+ leukemia cell death. Conversely, recombinant NGAL protected NGAL-R+ CLL cells against apoptosis by activating a STAT3/Mcl-1 signaling pathway. Our results suggest that NGAL and NGAL-R, overexpressed in untreated CLL, participate in the deregulation of the apoptotic machinery in CLL cells, and may be potential therapeutic clues for CLL treatment.

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“…VEGFR-2 is upregulated in endothelial cells of newly forming blood vessels within tumors and is commonly implicated in neovascularization. A recent study demonstrated that the α4β1-integrin is capable of VEGFR2 binding and activation, presenting a novel potential target for therapy (89). Alternatively, VEGFR-1 has relatively weak pro-angiogenic properties and can recruit and activate tumor-associated macrophages (TAMs) and myeloid cells, promoting tumor cell metastasis and proliferation [Figure 3; (90)].…”

Section: Metabolism Vascular Invasion and Immune Cells Within The Tmementioning

confidence: 99%

Comparative Approach to the Temporo-Spatial Organization of the Tumor Microenvironment

et al. 2019

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The complex ecosystem in which tumor cells reside and interact, termed the tumor microenvironment (TME), encompasses all cells and components associated with a neoplasm that are not transformed cells. Interactions between tumor cells and the TME are complex and fluid, with each facet coercing the other, largely, into promoting tumor progression. While the TME in humans is relatively well-described, a compilation and comparison of the TME in our canine counterparts has not yet been described. As is the case in humans, dog tumors exhibit greater heterogeneity than what is appreciated in laboratory animal models, although the current level of knowledge on similarities and differences in the TME between dogs and humans, and the practical implications of that information, require further investigation. This review summarizes some of the complexities of the human and mouse TME and interjects with what is known in the dog, relaying the information in the context of the temporo-spatial organization of the TME. To the authors' knowledge, the development of the TME over space and time has not been widely discussed, and a comprehensive review of the canine TME has not been done. The specific topics covered in this review include cellular invasion and interactions within the TME, metabolic derangements in the TME and vascular invasion, and the involvement of the TME in tumor spread and metastasis.

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α4β1 integrin associates with VEGFR2 in CLL cells and contributes to VEGF binding and intracellular signaling

Abstract: Key Points α4β1 integrin and VEGFR2 function as a receptor complex for VEGF in CLL cells. Contribution to VEGF functions in CLL is a novel pathological role for α4β1 integrin in this malignancy.

Cited by 9 publications

References 24 publications

Growth Factors VEGF-A165 and FGF-2 as Multifunctional Biomolecules Governing Cell Adhesion and Proliferation

Growth Factors VEGF-A165 and FGF-2 as Multifunctional Biomolecules Governing Cell Adhesion and Proliferation

Relation of Neutrophil Gelatinase-Associated Lipocalin Overexpression to the Resistance to Apoptosis of Tumor B Cells in Chronic Lymphocytic Leukemia

Comparative Approach to the Temporo-Spatial Organization of the Tumor Microenvironment

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