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@article{2250024,
author = {Čada, Štěpán and Vondálová Blanářová, Olga and Gömöryová, Kristína and Mikulová, Antónia and Bačovská, Petra and Zezula, Nikodém and Jadaun, Alka Kumari and Janovská, Pavlína and Plešingerová, Hana and Bryja, Vítězslav},
article_location = {Lausanne},
article_number = {December},
doi = {http://dx.doi.org/10.3389/fcell.2022.911966},
keywords = {amoeboid cell migration; chronic lymphocytic leukemia; mantle cell lymphoma; casein kinase 1; live imaging; B cells; uropod},
language = {eng},
issn = {2296-634X},
journal = {Frontiers in Cell and Developmental Biology},
title = {Role of casein kinase 1 in the amoeboid migration of B-cell leukemic and lymphoma cells: A quantitative live imaging in the confined environment},
url = {https://doi.org/10.3389/fcell.2022.911966},
volume = {10},
year = {2022}
}
TY - JOUR
ID - 2250024
AU - Čada, Štěpán - Vondálová Blanářová, Olga - Gömöryová, Kristína - Mikulová, Antónia - Bačovská, Petra - Zezula, Nikodém - Jadaun, Alka Kumari - Janovská, Pavlína - Plešingerová, Hana - Bryja, Vítězslav
PY - 2022
TI - Role of casein kinase 1 in the amoeboid migration of B-cell leukemic and lymphoma cells: A quantitative live imaging in the confined environment
JF - Frontiers in Cell and Developmental Biology
VL - 10
IS - December
SP - 1-22
EP - 1-22
PB - Frontiers Media S.A.
SN - 2296634X
KW - amoeboid cell migration
KW - chronic lymphocytic leukemia
KW - mantle cell lymphoma
KW - casein kinase 1
KW - live imaging
KW - B cells
KW - uropod
UR - https://doi.org/10.3389/fcell.2022.911966
N2 - The migratory properties of leukemic cells are commonly associated with their pathological potential and can significantly affect the disease progression. While the research in immunopathology mostly employed powerful indirect methods such as flow cytometry, these cells were rarely observed directly using live imaging microscopy. This is especially true for the malignant cells of the B-cell lineage, such as those originating from chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). In this study, we employed open-source image analysis tools to automatically and quantitatively describe the amoeboid migration of four B-cell leukemic and lymphoma cell lines and primary CLL cells. To avoid the effect of the shear stress of the medium on these usually non-adherent cells, we have confined the cells using a modified under-agarose assay. Surprisingly, the behavior of tested cell lines differed substantially in terms of basal motility or response to chemokines and VCAM1 stimulation. Since casein kinase 1 (CK1) was reported as a regulator of B-cell migration and a promoter of CLL, we looked at the effects of CK1 inhibition in more detail. Migration analysis revealed that CK1 inhibition induced rapid negative effects on the migratory polarity of these cells, which was quantitatively and morphologically distinct from the effect of ROCK inhibition. We have set up an assay that visualizes endocytic vesicles in the uropod and facilitates morphological analysis. This assay hints that the effect of CK1 inhibition might be connected to defects in polarized intracellular transport. In summary, 1) we introduce and validate a pipeline for the imaging and quantitative assessment of the amoeboid migration of CLL/MCL cells, 2) we provide evidence that the assay is sensitive enough to mechanistically study migration defects identified by the transwell assay, and 3) we describe the polarity defects induced by inhibition or deletion of CK1ε.
ER -
ČADA, Štěpán, Olga VONDÁLOVÁ BLANÁŘOVÁ, Kristína GÖMÖRYOVÁ, Antónia MIKULOVÁ, Petra BAČOVSKÁ, Nikodém ZEZULA, Alka Kumari JADAUN, Pavlína JANOVSKÁ, Hana PLEŠINGEROVÁ and Vítězslav BRYJA. Role of casein kinase 1 in the amoeboid migration of B-cell leukemic and lymphoma cells: A quantitative live imaging in the confined environment. \textit{Frontiers in Cell and Developmental Biology}. Lausanne: Frontiers Media S.A., 2022, vol.~10, December, p.~1-22. ISSN~2296-634X. Available from: https://dx.doi.org/10.3389/fcell.2022.911966.
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