PMID- 18373164
OWN - NLM
STAT- MEDLINE
DCOM- 20080617
LR  - 20211020
IS  - 0944-1174 (Print)
IS  - 0944-1174 (Linking)
VI  - 43
IP  - 3
DP  - 2008
TI  - Monocyte chemoattractant protein 1 and CD40 ligation have a synergistic effect on 
      vascular endothelial growth factor production through cyclooxygenase 2 
      upregulation in gastric cancer.
PG  - 216-24
LID - 10.1007/s00535-007-2151-8 [doi]
AB  - BACKGROUND: Recent studies have reported that expression of monocyte 
      chemoattractant protein 1 (MCP-1) and its receptor (CCR2) and CD40 ligation on 
      mesenchymal cells play important roles in tumor development. Cyclooxygenase 2 
      (COX-2) has also been shown to contribute to tumor angiogenesis. We examined the 
      interaction between MCP-1 and CD40 ligation in mesenchymal cells in gastric 
      cancer to determine the effect of these factors on vascular endothelial growth 
      factor (VEGF) production via upregulation of COX-2 expression. METHODS: COX-2, 
      prostaglandin E2 (PGE2), and VEGF production were evaluated in CD40 ligand 
      (CD40L)-stimulated macrophages. CD40L and MCP-1 mRNA levels in gastric cancer 
      tissues were evaluated by real-time polymerase chain reaction (PCR). 
      Localizations of MCP-1, CD40L, CD34, CD40, and CCR2 in 34 gastric cancer tissue 
      specimens were evaluated by single-or double-label immunohistochemistry. RESULTS: 
      COX-2 expression levels were significantly higher in CD40L-stimulated macrophages 
      and correlated with increased PGE2 and VEGF production. Addition of MCP-1 to 
      CD40L-stimulated macrophages had a synergistic effect on COX-2 expression and 
      subsequent PGE2 and VEGF production. CD40L and MCP-1 mRNA levels were 
      significantly higher in poorly differentiated gastric cancers than in H. 
      pylori-infected gastritis patients. High microvessel density was significantly 
      associated with MCP-1 and CCR2 scores and lymph node metastasis. CONCLUSIONS: 
      MCP-1 and CD40L had a synergistic effect on COX-2 expression and subsequent VEGF 
      production in gastric cancer.
FAU - Futagami, Seiji
AU  - Futagami S
AD  - Division of Gastroenterology, Department of Internal Medicine, Nippon Medical 
      School, 1-1-5 Sendagi, Tokyo, 113-8603, Japan.
FAU - Tatsuguchi, Atsushi
AU  - Tatsuguchi A
FAU - Hiratsuka, Tetsuro
AU  - Hiratsuka T
FAU - Shindo, Tomotaka
AU  - Shindo T
FAU - Horie, Akane
AU  - Horie A
FAU - Hamamoto, Tatsuhiko
AU  - Hamamoto T
FAU - Ueki, Nobue
AU  - Ueki N
FAU - Kusunoki, Masafumi
AU  - Kusunoki M
FAU - Miyake, Kazumasa
AU  - Miyake K
FAU - Gudis, Katya
AU  - Gudis K
FAU - Tsukui, Taku
AU  - Tsukui T
FAU - Sakamoto, Choitsu
AU  - Sakamoto C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080329
PL  - Japan
TA  - J Gastroenterol
JT  - Journal of gastroenterology
JID - 9430794
RN  - 0 (CCR2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 147205-72-9 (CD40 Ligand)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Adenocarcinoma/pathology
MH  - Adult
MH  - Aged
MH  - CD40 Ligand/*metabolism
MH  - Chemokine CCL2/*metabolism
MH  - Cyclooxygenase 2/genetics/*metabolism
MH  - Female
MH  - Gastritis/microbiology/pathology
MH  - Humans
MH  - Immunohistochemistry
MH  - Lymphatic Metastasis
MH  - Macrophages/metabolism
MH  - Male
MH  - Mesoderm/cytology/pathology
MH  - Middle Aged
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/metabolism
MH  - Receptors, CCR2/metabolism
MH  - Stomach Neoplasms/*pathology
MH  - Up-Regulation
MH  - Vascular Endothelial Growth Factor A/*metabolism
EDAT- 2008/04/01 09:00
MHDA- 2008/06/18 09:00
CRDT- 2008/04/01 09:00
PHST- 2007/03/29 00:00 [received]
PHST- 2007/12/24 00:00 [accepted]
PHST- 2008/04/01 09:00 [pubmed]
PHST- 2008/06/18 09:00 [medline]
PHST- 2008/04/01 09:00 [entrez]
AID - 10.1007/s00535-007-2151-8 [doi]
PST - ppublish
SO  - J Gastroenterol. 2008;43(3):216-24. doi: 10.1007/s00535-007-2151-8. Epub 2008 Mar 
      29.