PMID- 18292560
OWN - NLM
STAT- MEDLINE
DCOM- 20080813
LR  - 20191210
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 180
IP  - 5
DP  - 2008 Mar 1
TI  - Glycosylation-dependent interactions of C-type lectin DC-SIGN with colorectal 
      tumor-associated Lewis glycans impair the function and differentiation of 
      monocyte-derived dendritic cells.
PG  - 3347-56
AB  - Dendritic cells (DCs) are APCs that play an essential role by bridging innate and 
      adaptive immunity. DC-specific intercellular adhesion molecule-3-grabbing 
      nonintegrin (DC-SIGN) is one of the major C-type lectins expressed on DCs and 
      exhibits high affinity for nonsialylated Lewis (Le) glycans. Recently, we 
      reported the characterization of oligosaccharide ligands expressed on SW1116, a 
      typical human colorectal carcinoma recognized by mannan-binding protein, which is 
      a serum C-type lectin and has similar carbohydrate-recognition specificities as 
      DC-SIGN. These tumor-specific oligosaccharide ligands were shown to comprise 
      clusters of tandem repeats of Lea/Leb epitopes. In this study, we show that 
      DC-SIGN is involved in the interaction of DCs with SW1116 cells through the 
      recognition of aberrantly glycosylated forms of Lea/Leb glycans on 
      carcinoembryonic Ag (CEA) and CEA-related cell adhesion molecule 1 (CEACAM1). 
      DC-SIGN ligands containing Lea/Leb glycans are also highly expressed on primary 
      cancer colon epithelia but not on normal colon epithelia, and DC-SIGN is 
      suggested to be involved in the association between DCs and colorectal cancer 
      cells in situ by DC-SIGN recognizing these cancer-related Le glycan ligands. 
      Furthermore, when monocyte-derived DCs (MoDCs) were cocultured with SW1116 cells, 
      LPS-induced immunosuppressive cytokines such as IL-6 and IL-10 were increased. 
      The effects were significantly suppressed by blocking Abs against DC-SIGN. 
      Strikingly, LPS-induced MoDC maturation was inhibited by supernatants of 
      cocultures with SW1116 cells. Our findings imply that colorectal carcinomas 
      affecting DC function and differentiation through interactions between DC-SIGN 
      and colorectal tumor-associated Le glycans may induce generalized failure of a 
      host to mount an effective antitumor response.
FAU - Nonaka, Motohiro
AU  - Nonaka M
AD  - Research Center for Glycobiotechnology, Department of Molecular Physiology, 
      College of Information Science and Engineering, Ritsumeikan University, Shiga, 
      Japan.
FAU - Ma, Bruce Yong
AU  - Ma BY
FAU - Murai, Ryuuya
AU  - Murai R
FAU - Nakamura, Natsuko
AU  - Nakamura N
FAU - Baba, Makoto
AU  - Baba M
FAU - Kawasaki, Nobuko
AU  - Kawasaki N
FAU - Hodohara, Keiko
AU  - Hodohara K
FAU - Asano, Shinji
AU  - Asano S
FAU - Kawasaki, Toshisuke
AU  - Kawasaki T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Antigens, Tumor-Associated, Carbohydrate)
RN  - 0 (CA-19-9 Antigen)
RN  - 0 (CD66 antigens)
RN  - 0 (Carcinoembryonic Antigen)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (DC-specific ICAM-3 grabbing nonintegrin)
RN  - 0 (Glycosphingolipids)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Lewis Blood Group Antigens)
RN  - 0 (Ligands)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (disialyl Lewis a antigen)
RN  - 139568-87-9 (trifucosyl-Lewis-b antigen)
SB  - IM
MH  - Antigens, CD/metabolism
MH  - Antigens, Neoplasm/*metabolism
MH  - Antigens, Tumor-Associated, Carbohydrate/*metabolism
MH  - CA-19-9 Antigen
MH  - Carcinoembryonic Antigen/metabolism
MH  - Carcinoma, Hepatocellular/metabolism/pathology
MH  - Cell Adhesion Molecules/*metabolism
MH  - Cell Differentiation/*immunology
MH  - Cell Line, Tumor
MH  - Cell-Free System/immunology/metabolism/pathology
MH  - Coculture Techniques
MH  - Colorectal Neoplasms/immunology/*metabolism/pathology
MH  - Dendritic Cells/*immunology/*pathology
MH  - Glycosphingolipids/*metabolism
MH  - Glycosylation
MH  - Humans
MH  - Lectins, C-Type/*metabolism
MH  - Lewis Blood Group Antigens
MH  - Ligands
MH  - Liver Neoplasms/metabolism/pathology
MH  - Monocytes/metabolism/pathology
MH  - Receptors, Cell Surface/*metabolism
MH  - U937 Cells
EDAT- 2008/02/23 09:00
MHDA- 2008/08/14 09:00
CRDT- 2008/02/23 09:00
PHST- 2008/02/23 09:00 [pubmed]
PHST- 2008/08/14 09:00 [medline]
PHST- 2008/02/23 09:00 [entrez]
AID - 180/5/3347 [pii]
AID - 10.4049/jimmunol.180.5.3347 [doi]
PST - ppublish
SO  - J Immunol. 2008 Mar 1;180(5):3347-56. doi: 10.4049/jimmunol.180.5.3347.