CXCR4 Mediates Enhanced Cell Migration in CALM-AF10 Leukemia

Fertal, Shelby A.; Zaidi, Sayyed K.; Stein, Janet L.; Heath, Jessica L.

doi:10.3389/fonc.2021.708915

Cited by 2 publications

(1 citation statement)

References 43 publications

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“…S1B-G). AML cell lines express consistently CD74, CD44, and CXCR4 [27][28][29]. The expression of CXCR2, a noncognate receptor for MIF [10], was analyzed in a few samples and was not consistently detectable on either blasts or MΦ.…”

Section: Mif Inhibition Induces Aml Blast Apoptosis But Bm Cells Are ...mentioning

confidence: 99%

Macrophage migration inhibitory factor blockade reprograms macrophages and disrupts prosurvival signaling in acute myeloid leukemia

Spertini,

Bénéchet,

Birch

et al. 2024

Cell Death Discov.

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The malignant microenvironment plays a major role in the development of resistance to therapies and the occurrence of relapses in acute myeloid leukemia (AML). We previously showed that interactions of AML blasts with bone marrow macrophages (MΦ) shift their polarization towards a protumoral (M2-like) phenotype, promoting drug resistance; we demonstrated that inhibiting the colony-stimulating factor-1 receptor (CSF1R) repolarizes MΦ towards an antitumoral (M1-like) phenotype and that other factors may be involved. We investigated here macrophage migration inhibitory factor (MIF) as a target in AML blast survival and protumoral interactions with MΦ. We show that pharmacologically inhibiting MIF secreted by AML blasts results in their apoptosis. However, this effect is abrogated when blasts are co-cultured in close contact with M2-like MΦ. We next demonstrate that pharmacological inhibition of MIF secreted by MΦ, in the presence of granulocyte macrophage-colony stimulating factor (GM-CSF), efficiently reprograms MΦ to an M1-like phenotype that triggers apoptosis of interacting blasts. Furthermore, contact with reprogrammed MΦ relieves blast resistance to venetoclax and midostaurin acquired in contact with CD163+ protumoral MΦ. Using intravital imaging in mice, we also show that treatment with MIF inhibitor 4-IPP and GM-CSF profoundly affects the tumor microenvironment in vivo: it strikingly inhibits tumor vasculature, reduces protumoral MΦ, and slows down leukemia progression. Thus, our data demonstrate that MIF plays a crucial role in AML MΦ M2-like protumoral phenotype that can be reversed by inhibiting its activity and suggest the therapeutic targeting of MIF as an avenue towards improved AML treatment outcomes.

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Section: Mif Inhibition Induces Aml Blast Apoptosis But Bm Cells Are ...mentioning

confidence: 99%

Macrophage migration inhibitory factor blockade reprograms macrophages and disrupts prosurvival signaling in acute myeloid leukemia

Spertini,

Bénéchet,

Birch

et al. 2024

Cell Death Discov.

View full text Add to dashboard Cite

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Current methods for studying metastatic potential of tumor cells

Bouchalová

Bouchal

2022

Cancer Cell Int

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Cell migration and invasiveness significantly contribute to desirable physiological processes, such as wound healing or embryogenesis, as well as to serious pathological processes such as the spread of cancer cells to form tumor metastasis. The availability of appropriate methods for studying these processes is essential for understanding the molecular basis of cancer metastasis and for identifying suitable therapeutic targets for anti-metastatic treatment. This review summarizes the current status of these methods: In vitro methods for studying cell migration involve two-dimensional (2D) assays (wound-healing/scratch assay), and methods based on chemotaxis (the Dunn chamber). The analysis of both cell migration and invasiveness in vitro require more complex systems based on the Boyden chamber principle (Transwell migration/invasive test, xCELLigence system), or microfluidic devices with three-dimensional (3D) microscopy visualization. 3D culture techniques are rapidly becoming routine and involve multicellular spheroid invasion assays or array chip-based, spherical approaches, multi-layer/multi-zone culture, or organoid non-spherical models, including multi-organ microfluidic chips. The in vivo methods are mostly based on mice, allowing genetically engineered mice models and transplant models (syngeneic mice, cell line-derived xenografts and patient-derived xenografts including humanized mice models). These methods currently represent a solid basis for the state-of-the art research that is focused on understanding metastatic fundamentals as well as the development of targeted anti-metastatic therapies, and stratified treatment in oncology.

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CXCR4 Mediates Enhanced Cell Migration in CALM-AF10 Leukemia

Cited by 2 publications

References 43 publications

Macrophage migration inhibitory factor blockade reprograms macrophages and disrupts prosurvival signaling in acute myeloid leukemia

Macrophage migration inhibitory factor blockade reprograms macrophages and disrupts prosurvival signaling in acute myeloid leukemia

Current methods for studying metastatic potential of tumor cells

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