Tunneling nanotubes facilitate autophagosome transfer in the leukemic niche

Rooij, Bob de; Polak, Roel; Stalpers, Femke; Pieters, Rob; Boer, Monique L. den

doi:10.1038/leu.2017.117

Cited by 46 publications

(45 citation statements)

References 16 publications

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“…However, the source of MMP-9 may also lie in the BMM, as our data show. Further, our findings are consistent with several other studies demonstrating the ability of leukemia cells to remodel the BMM into a leukemia-promoting and -perpetuating niche via the release of cytokines [2,3,39], extracellular vesicles [40] or other pathways [41]. Whether our observations are specific to BCR-ABL1 + leukemia will be assessed in future.…”

Section: Discussionsupporting

confidence: 91%

Bone marrow niche-derived extracellular matrix-degrading enzymes influence the progression of B-cell acute lymphoblastic leukemia

et al. 2020

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Specific and reciprocal interactions with the bone marrow microenvironment (BMM) govern the course of hematological malignancies. Matrix metalloproteinase-9 (MMP-9), secreted by leukemia cells, facilitates tumor progression via remodeling of the extracellular matrix (ECM) of the BMM. Hypothesizing that leukemias may instruct the BMM to degrade the ECM, we show, that MMP-9-deficiency in the BMM prolongs survival of mice with BCR-ABL1-induced B-cell acute lymphoblastic leukemia (B-ALL) compared with controls and reduces leukemia-initiating cells. MMP-9-deficiency in the BMM leads to reduced degradation of proteins of the ECM and reduced invasion of BALL. Using various in vivo and in vitro assays, as well as recipient mice deficient for the receptor for tumor necrosis factor (TNF) α (TNFR1) we demonstrate that BALL cells induce MMP-9-expression in mesenchymal stem cells (MSC) and possibly other cells of the BMM via a release of TNFα. MMP-9-expression in MSC is mediated by activation of nuclear factor kappa B (NF-κB) downstream of TNFR1. Consistently, knockdown of TNF-α in BALL initiating cells or pharmacological inhibition of MMP-9 led to significant prolongation of survival in mice with BALL. In summary, leukemia cell-derived Tnfα induced MMP-9-expression by the BMM promoting BALL progression. Inhibition of MMP-9 may act as an adjunct to existing therapies.

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Section: Discussionsupporting

confidence: 91%

Bone marrow niche-derived extracellular matrix-degrading enzymes influence the progression of B-cell acute lymphoblastic leukemia

et al. 2020

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“…This mode of intercellular signaling leads to the secretion of prosurvival cytokines and chemotactic proteins, as well as the development of resistance to prednisolone, a drug frequently used for the treatment of B-ALL. Accordingly, the blockade of TNT inhibits leukemic progression and prednisolone resistance that is mediated by the stroma (de Rooij et al, 2017;Polak et al, 2015) (see poster). Furthermore, a mitochondrial transfer to leukemic cells (AML cells) but not nonmalignant CD34 cells by stromal cells leads to increased chemoresistance through the increased production of mitochondrial adenosine triphosphate and decreased propensity to depolarization of mitochondria after chemotherapy (Moschoi et al, 2016).…”

Section: Alteration Of the Bmm By Malignant Hematopoietic Cellsmentioning

confidence: 99%

The bone marrow microenvironment in health and disease at a glance

Kumar

Godavarthy

Krause

2018

Journal of Cell Science

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The bone marrow microenvironment (BMM) is the 'domicile' of hematopoietic stem cells, as well as of malignant processes that can develop there. Multiple and complex interactions with the BMM influence hematopoietic stem cell (HSC) physiology, but also the pathophysiology of hematological malignancies. Reciprocally, hematological malignancies alter the BMM, in order to render it more hospitable for malignant progression. In this Cell Science at a Glance article and accompanying poster, we highlight concepts of the normal and malignant hematopoietic stem cell niches. We present the intricacies of the BMM in malignancy and provide approaches for targeting the interactions between malignant cells and their BMM. This is done in an effort to augment existing treatment strategies in the future.

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“…In addition, several teams describe that TNTs also allow tumor cells to reprogram the healthy neighboring cells to make them more conducive to the formation of a tumor niche. Interestingly, not only a hostile environment (inflammation, hypoxia, and inadequate pH) enhances TNT formation [4,[8][9][10][11], but also TNTs could contribute to the escape of the cells from the cell death induced by apoptosis [10,[12][13][14]. On the other hand, TNTs convey resistance to chemotherapy by exporting the mitochondria [15,16].…”

Section: Introductionmentioning

confidence: 99%

Investigating Tunneling Nanotubes in Cancer Cells: Guidelines for Structural and Functional Studies through Cell Imaging

Dubois

Bénard

Jean-Jacques

et al. 2020

BioMed Research International

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By allowing insured communication between cancer cells themselves and with the neighboring stromal cells, tunneling nanotubes (TNTs) are involved in the multistep process of cancer development from tumorigenesis to the treatment resistance. However, despite their critical role in the biology of cancer, the study of the TNTs has been announced challenging due to not only the absence of a specific biomarker but also the fragile and transitory nature of their structure and the fact that they are hovering freely above the substratum. Here, we proposed to review guidelines to follow for studying the structure and functionality of TNTs in tumoral neuroendocrine cells (PC12) and nontumorigenic human bronchial epithelial cells (HBEC-3, H28). In particular, we reported how crucial is it (i) to consider the culture conditions (culture surface, cell density), (ii) to visualize the formation of TNTs in living cells (mechanisms of formation, 3D representation), and (iii) to identify the cytoskeleton components and the associated elements (categories, origin, tip, and formation/transport) in the TNTs. We also focused on the input of high-resolution cell imaging approaches including Stimulated Emission Depletion (STED) nanoscopy, Transmitted and Scanning Electron Microscopies (TEM and SEM). In addition, we underlined the important role of the organelles in the mechanisms of TNT formation and transfer between the cancer cells. Finally, new biological models for the identification of the TNTs between cancer cells and stromal cells (liquid air interface, ex vivo, in vivo) and the clinical considerations will also be discussed.

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Tunneling nanotubes facilitate autophagosome transfer in the leukemic niche

Cited by 46 publications

References 16 publications

Bone marrow niche-derived extracellular matrix-degrading enzymes influence the progression of B-cell acute lymphoblastic leukemia

Bone marrow niche-derived extracellular matrix-degrading enzymes influence the progression of B-cell acute lymphoblastic leukemia

The bone marrow microenvironment in health and disease at a glance

Investigating Tunneling Nanotubes in Cancer Cells: Guidelines for Structural and Functional Studies through Cell Imaging

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