PMID- 22056877
OWN - NLM
STAT- MEDLINE
DCOM- 20120905
LR  - 20211021
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 31
IP  - 26
DP  - 2012 Jun 28
TI  - Chitinase 3-like 1 promotes macrophage recruitment and angiogenesis in colorectal 
      cancer.
PG  - 3111-23
LID - 10.1038/onc.2011.498 [doi]
AB  - Chitinase 3-like 1 (CHI3L1), one of the mammalian members of the chitinase 
      family, is expressed in several types of human cancer, and elevated serum level 
      of CHI3L1 is suggested to be a biomarker of poor prognosis in advanced cancer 
      patients. However, the overall biological function of CHI3L1 in human cancers 
      still remains unknown. Studies were performed to characterize the role of CHI3L1 
      in cancer pathophysiology utilizing human colorectal cancer samples and human 
      cell lines. Plasma protein and tissue mRNA expression levels of CHI3L1 in 
      colorectal cancer were strongly upregulated. Immunohistochemical analysis showed 
      that CHI3L1 was expressed in cancer cells, and CHI3L1 expression had a 
      significant association with the number of infiltrated macrophages and 
      microvessel density (MVD). By utilizing transwell migration and tube-formation 
      assays, overexpression of CHI3L1 in SW480 cells (human colon cancer cells) 
      enhanced the migration of THP-1 cells (human macrophage cells) and HUVECs (human 
      endothelial cells), and the tube formation of HUVECs. The knockdown of CHI3L1 by 
      RNA interference or the neutralization of CHI3L1 by anti-CHI3L1 antibody 
      displayed strong suppression of CHI3L1-induced migration and tube formation. Cell 
      proliferation assay showed that CHI3L1 overexpression significantly enhanced the 
      proliferation of SW480 cells. Enzyme-linked immunosorbent assay (ELISA) analysis 
      showed that CHI3L1 increased the secretion of inflammatory chemokines, IL-8 and 
      monocyte chemoattractant protein-1 (MCP-1), from SW480 cells through 
      mitogen-activated protein kinase (MAPK) signaling pathway. Both neutralization of 
      IL-8 or MCP-1 and inhibition or knockdown of MAPK in SW480 cells significantly 
      inhibited CHI3L1-induced migration and tube formation. In a xenograft mouse 
      model, overexpression of CHI3L1 in HCT116 cells (human colon cancer cells) 
      enhanced the tumor growth as well as macrophage infiltration and MVD. In 
      conclusion, CHI3L1 expressed in colon cancer cells promotes cancer cell 
      proliferation, macrophage recruitment and angiogenesis. Thus, the inhibition of 
      CHI3L1 activity may be a novel therapeutic strategy for human colorectal cancer.
FAU - Kawada, M
AU  - Kawada M
AD  - Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto 
      University, Kyoto, Japan. kawadam@kuhp.kyoto-u.ac.jp
FAU - Seno, H
AU  - Seno H
FAU - Kanda, K
AU  - Kanda K
FAU - Nakanishi, Y
AU  - Nakanishi Y
FAU - Akitake, R
AU  - Akitake R
FAU - Komekado, H
AU  - Komekado H
FAU - Kawada, K
AU  - Kawada K
FAU - Sakai, Y
AU  - Sakai Y
FAU - Mizoguchi, E
AU  - Mizoguchi E
FAU - Chiba, T
AU  - Chiba T
LA  - eng
GR  - P30 DK043351/DK/NIDDK NIH HHS/United States
GR  - R01 DK080070/DK/NIDDK NIH HHS/United States
GR  - R01 DK080070-01A2/DK/NIDDK NIH HHS/United States
GR  - R01DK80070/DK/NIDDK NIH HHS/United States
GR  - R01 DK080070-01A2S1/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111107
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Adipokines)
RN  - 0 (CCL2 protein, human)
RN  - 0 (CHI3L1 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chitinase-3-Like Protein 1)
RN  - 0 (Interleukin-8)
RN  - 0 (Lectins)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Adipokines/genetics/*metabolism
MH  - Aged
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Cell Transformation, Neoplastic
MH  - Chemokine CCL2/metabolism
MH  - Chemotaxis
MH  - Chitinase-3-Like Protein 1
MH  - Colorectal Neoplasms/blood supply/immunology/*metabolism/*pathology
MH  - Disease Progression
MH  - Endothelial Cells/metabolism/pathology
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Interleukin-8/metabolism
MH  - Lectins/genetics/*metabolism
MH  - MAP Kinase Signaling System
MH  - Macrophages/*cytology/*immunology
MH  - Mice
MH  - Middle Aged
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Neovascularization, Pathologic/*metabolism/pathology
MH  - Tumor Microenvironment
PMC - PMC3290745
MID - NIHMS328968
COIS- Conflicts of interest The authors declare no conflict of interest.
EDAT- 2011/11/08 06:00
MHDA- 2012/09/06 06:00
PMCR- 2012/12/28
CRDT- 2011/11/08 06:00
PHST- 2011/11/08 06:00 [entrez]
PHST- 2011/11/08 06:00 [pubmed]
PHST- 2012/09/06 06:00 [medline]
PHST- 2012/12/28 00:00 [pmc-release]
AID - onc2011498 [pii]
AID - 10.1038/onc.2011.498 [doi]
PST - ppublish
SO  - Oncogene. 2012 Jun 28;31(26):3111-23. doi: 10.1038/onc.2011.498. Epub 2011 Nov 7.