Biomechanical alterations of dendritic cells by co-culturing with K562 CML cells and their potential role in immune escape.
Dendritic cells (DCs), which are potent antigen presenting cells (APCs), are utilized to deliver the signals essential for the initiation of immune responses. In this study, we used an interdisciplinary approach to characterize the effect of K562 cells, a human chronic myeloid leukemia (CML) cell line, on the biomechanical characteristics and immune functions of DCs. When co-cultured with K562 cells, the biomechanical and immunological characteristics of immature DCs (imDCs) and mature DCs (mDCs) were severely impaired compared with controls. The changes include increased membrane viscoelasticity, reorganized cytoskeleton (F-actin), suppressed capability of antigen uptake, transendothelium migration, and activation of naïve T cells. In exploring the mechanisms of these changes, we identified several genes and proteins by microarray analysis and 2D gel electrophoresis. Changes were found in the cytoskeleton-related genes and proteins (such as cofilin1 and profilin1) and matrix-related genes and proteins (such as TIMP1 and MMP9). These findings provide a molecular basis for the biomechanical and immunological changes of DCs in response to K562 and may help to elucidate the mechanism for tumor immune escape.
Xu
Xiaofeng
X
Department of Laboratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, PR China.
Zeng
Zhu
Z
Yao
Weijuan
W
Wang
Xianwei
X
Sun
Dagong
D
Ka
Weibo
W
Zhang
Yingyu
Y
Wang
Xifu
X
Chen
Xiaopeng
X
Zha
Yi
Y
Sun
Li
L
Xie
Lide
L
Wen
Zongyao
Z
Chien
Shu
S
D000199:Actins / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D001696:Biomechanical Phenomena; D002454:Cell Differentiation; D002465:Cell Movement; D018920:Coculture Techniques; D051338:Cofilin 1 / Q000235:genetics; D017077:Culture Media, Conditioned; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000502:physiology*; D004548:Elasticity; D004705:Endocytosis; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D051304:Profilins / Q000235:genetics; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D019139:Tumor Escape; D014783:Viscosity
D000199:Actins; D015703:Antigens, CD; C495810:CFL1 protein, human; D051338:Cofilin 1; D017077:Culture Media, Conditioned; C495738:PFN1 protein, human; D051304:Profilins; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9