The CCL2/CCR2 Axis Affects Transmigration and Proliferation but Not Resistance to Chemotherapy of Acute Myeloid Leukemia Cells

Autor: Bruno Nervi, Patricia Macanas-Pirard, Thomas Quezada, Pablo Ramirez, Andrea V. Leisewitz, Richard Broekhuizen, Leonardo Navarrete
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Myeloid
animal diseases
Cancer Treatment
lcsh:Medicine
Apoptosis
Monocytes
Hematologic Cancers and Related Disorders
chemistry.chemical_compound
Mice
Leukemia
Promyelocytic
Acute
Bone Marrow
Cell Movement
hemic and lymphatic diseases
Medicine and Health Sciences
lcsh:Science
Chemokine CCL2
Cultured Tumor Cells
Aged
80 and over
Multidisciplinary
Cell Death
Pharmaceutics
Gene Expression Regulation
Leukemic
Myeloid leukemia
hemic and immune systems
Hematology
Animal Models
U937 Cells
Cell cycle
Middle Aged
Myeloid Leukemia
Flow Cytometry
Leukemia
Cell Motility
Leukemia
Myeloid
Acute
medicine.anatomical_structure
Oncology
Experimental Organism Systems
Cell Processes
Biological Cultures
Research Article
Acute Myeloid Leukemia
Clinical Oncology
Adult
Adolescent
Receptors
CCR2
Mouse Models
Enzyme-Linked Immunosorbent Assay
Cell Migration
Biology
Research and Analysis Methods
Colony-Forming Units Assay
03 medical and health sciences
Cancer Chemotherapy
Young Adult
Model Organisms
Drug Therapy
Cell Line
Tumor
parasitic diseases
Leukemias
medicine
Chemotherapy
Animals
Humans
Propidium iodide
Leukemia Cells
Aged
Cell Proliferation
Cell growth
lcsh:R
Cancers and Neoplasms
Biology and Life Sciences
Cell Biology
Cell Cultures
medicine.disease
Transplantation
Mice
Inbred C57BL
030104 developmental biology
chemistry
Drug Resistance
Neoplasm
Cancer research
lcsh:Q
Bone marrow
Clinical Medicine
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Vol 12, Iss 1, p e0168888 (2017)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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