Myosin IIa activation is crucial in breast cancer derived galectin-1 mediated tolerogenic dendritic cell differentiation.
BACKGROUND
Tolerogenic dendritic cells (tDCs) play important roles in immune tolerance, autoimmune disease, tissue transplantation, and the tumor micro-environment. Factors that induce tDCs have been reported, however the intracellular mechanisms involved are rarely discussed.


METHODS
Circulating CD14(+)CD16(+) of breast cancer patients and induced CD14(+)CD16(+) DCs were identified as tDCs by treating CD14(+) monocytes with galectin-1 and cancer cell-derived medium combined with IL-4 and GM-CSF. In addition, the 4T1 breast cancer syngeneic xenograft model was used to investigate the effect of galectin-1 in vivo.


RESULTS
The CD14(+)CD16(+) tDC population in the breast cancer patients was comparatively higher than that in the healthy donors, and both the MDA-MB-231 conditioned medium and galectin-1 could induce tDC differentiation. In a BALB/c animal model, the 4T1 breast cancer cell line enhanced IL-10 expression in CD11c(+) DCs which was down-regulated after knocking down the galectin-1 expression of 4T1 cells. Analysis of galectin-1 interacting proteins showed that myosin IIa was a major target of galectin-1 after internalization through a caveolin-dependent endocytosis. Myosin IIa specific inhibitor could diminish the effects of galectin-1 on monocyte-derived tDCs and also block the 4T1 cell induced CD11c(+)/Ly6G(+)/IL-10(+) in the BALB/c mice.


CONCLUSIONS
Galectin-1 can induce tDCs after internalizing into CD14(+) monocytes through the caveolae-dependent pathway and activating myosin IIa. For the breast cancer patients with a high galectin-1 expression, blebbistatin and genistein show potential in immune modulation and cancer immunotherapy.


CONCLUSIONS
Myosin IIa activation and galectin-1 endocytosis are important in tumor associated tDC development.
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Da-En
DE
Cheng
School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Jen-Yu
JY
Hung
School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Ming-Shyan
MS
Huang
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Ya-Ling
YL
Hsu
Department of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan; Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Chi-Yu
CY
Lu
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Eing-Mei
EM
Tsai
Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: mifeho@kmu.edu.tw.
Ming-Feng
MF
Hou
Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Electronic address: kuopolin@seed.net.tw.
Po-Lin
PL
Kuo
D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology*; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology*; D004705:Endocytosis; D005260:Female; D037483:Galectin 1 / Q000502:physiology*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D024507:Nonmuscle Myosin Type IIA / Q000502:physiology*
D037483:Galectin 1; D006576:Heterocyclic Compounds, 4 or More Rings; C472645:blebbistatin; D024507:Nonmuscle Myosin Type IIA
Breast cancer; Dendritic cell; Endocytosis; Galectin-1; Myosin IIa