ArticlePloS one2017
The CCL2/CCR2 Axis Affects Transmigration and Proliferation but Not Resistance to Chemotherapy of Acute Myeloid Leukemia Cells.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 68 citations in OpenAlex.
- From bud to stem: dynamics of hematopoietic stem cells that drive homing and mobilization.Current opinion in hematology · 2026Review
- Regulatory role of mTORC1 signaling in osteoblasts in acute myeloid leukemia progression and steady-state hematopoiesis.iScience · 2026Article
- Convergent Multistage Evidence Implicates the CCR2-Artemin Immune-Inflammation Axis in Acute Myeloid Leukemia.Mediators of inflammation · 2026Article
- Leveraging Targeted Protein Degradation for G Protein-Coupled Receptors: The Development of CCR2 Molecular Degraders.Journal of medicinal chemistry · 2025Article
- CCL2/CCR2 signaling pathway in tumorigenesis and metastasis (Review).Oncology letters · 2025Review
- Dual Roles of CD147 in Regulating THP-1 Monocyte Migration and MCP-1-Induced Inflammatory Responses.International journal of molecular sciences · 2025Article
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- The power of many: Multilevel targeting of representative chemokine and metabolite GPCRs in personalized cancer therapy.European journal of immunology · 2024Review
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- CCR2 cooperativity promotes hematopoietic stem cell homing to the bone marrow.Science advances · 2024Article
- The complex role of macrophages in pancreatic cancer tumor microenvironment: a review on cancer progression and potential therapeutic targets.Discover oncology · 2024Review
- Targeting CCL2/CCR2 Signaling Overcomes MEK Inhibitor Resistance in Acute Myeloid Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Multiple roles for AU-rich RNA binding proteins in the development of haematologic malignancies and their resistance to chemotherapy.RNA biology · 2024Review
- Alpha-synuclein shapes monocyte and macrophage cell biology and functions by bridging alterations of autophagy and inflammatory pathways.Frontiers in cell and developmental biology · 2024Article
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- The role and therapeutic targeting of the CCL2/CCR2 signaling axis in inflammatory and fibrotic diseases.Frontiers in immunology · 2024Review
- Article
- Functionally Relevant Cytokine/Receptor Axes in Myelofibrosis.Biomedicines · 2023Review
- The role of CD180 in hematological malignancies and inflammatory disorders.Molecular medicine (Cambridge, Mass.) · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute myeloid leukemia (AML) has a high mortality rate despite chemotherapy and transplantation. Both CXCR4/SDF-1 and VLA-4/VCAM1 axes are involved in leukemia protection but little is known about the role of CCL2/CCR2 in AML biology and protection against chemotherapy. We measured CCR2 expression in AML cell lines and primary AML cells by flow cytometry (FCM), real time PCR (RT-PCR) and western blot (WB). CCL2 production was quantified by solid phase ELISA in peripheral blood (PB) and bone marrow (BM) serum. We measured chemotaxis in a transwell system with different concentrations of CCL2/CCR2 blockers; cell cycle with BrDU and propidium iodide and proliferation with yellow tetrazolium MTT. We determined synergy in in vitro cell apoptosis combining chemotherapy and CCL2/CCR2 blockade. Finally, we performed chemoprotection studies in an in vivo mouse model. Of 35 patients, 23 (65%) expressed CCR2 by FCM in PB. Two cell lines expressed high levels of CCR2 (THP-1 and murine AML). RT-PCR and WB confirmed CCR2 production. CCL2 solid phase ELISA showed significantly lower levels of CCL2 in PB and BM compared to normal controls. Chemotaxis experiments confirmed a dose-dependent migration in AML primary cells expressing CCR2 and THP-1 cells. A significant inhibition of transmigration was seen after CCL2/CCR2 blockade. Proliferation of CCR2+ AML cell lines was slightly increased (1.4-fold) after axis stimulation. We observed a non-significant increase in phase S THP-1 cells exposed to CCL2 and a concomitant decrease of cells in G1. The chemotherapy studies did not show a protective effect of CCL2 on cytarabine-induced apoptosis or synergy with chemotherapy after CCL2/CCR2 blockade both in vitro and in vivo. In conclusion, CCL2/CCR2 axis is expressed in the majority of monocytoid AML blasts. The axis is involved in cell trafficking and proliferation but no in vitro and in vivo chemotherapy protective effect was seen.
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