PMID- 16278381
OWN - NLM
STAT- MEDLINE
DCOM- 20060404
LR  - 20061115
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 11
IP  - 21
DP  - 2005 Nov 1
TI  - Monocyte chemoattractant protein-1 transfection induces angiogenesis and 
      tumorigenesis of gastric carcinoma in nude mice via macrophage recruitment.
PG  - 7629-36
AB  - PURPOSE: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that has 
      various roles in tumor development and progression. We previously reported that 
      expression of MCP-1 is associated with macrophage infiltration and tumor vessel 
      density in human gastric carcinomas. The present study was undertaken to obtain 
      direct evidence that MCP-1 participates in recruitment of macrophages and 
      induction of angiogenesis. EXPERIMENTAL DESIGN: We did transfection experiments 
      to analyze the role of MCP-1 in tumorigenicity and angiogenesis in gastric 
      carcinoma in nude mice. The human MCP-1 gene cloned into the BCMGS-Neo expression 
      vector was transfected into the human gastric carcinoma TMK-1 cell line. We 
      examined tumor volumes with the ectopic s.c. xenograft model and tumorigenicity 
      with the orthotopic gastric xenograft model. We determined intratumor microvessel 
      counts and tumor-infiltrating macrophage counts by immunohistochemical staining. 
      RESULTS: There was no difference in in vitro proliferation between 
      MCP-1-transfected TMK-1 cells and mock-transfected (control) cells; however, 
      MCP-1 transfectants induced tumor growth in ectopic xenografts and increased 
      tumorigenicity and induced lymph node metastases and ascites in orthotopic 
      xenografts. In both ectopic and orthotopic xenograft models, strong infiltration 
      of macrophages was observed within and around the tumors after implantation of 
      MCP-1 transfectants whereas fewer macrophages were seen after inoculation of 
      control cells. The microvessel density was significantly higher in tumors 
      produced by MCP-1 transfectants than in control tumors. CONCLUSIONS: MCP-1 
      produced by gastric carcinoma cells may regulate angiogenesis via macrophage 
      recruitment. MCP-1 may be a potential target for antiangiogenic therapy for 
      gastric carcinoma.
FAU - Kuroda, Tsuyoshi
AU  - Kuroda T
AD  - Department of Medicine and Molecular Science, Graduate School of Biomedical 
      Sciences and Health Service Center, Hiroshima University, Japan.
FAU - Kitadai, Yasuhiko
AU  - Kitadai Y
FAU - Tanaka, Shinji
AU  - Tanaka S
FAU - Yang, Xiaoqin
AU  - Yang X
FAU - Mukaida, Naofumi
AU  - Mukaida N
FAU - Yoshihara, Masaharu
AU  - Yoshihara M
FAU - Chayama, Kazuaki
AU  - Chayama K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA Primers)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Chemokine CCL2/*biosynthesis/*genetics/*physiology
MH  - DNA Primers/chemistry
MH  - Disease Progression
MH  - Enzyme-Linked Immunosorbent Assay
MH  - *Gene Expression Regulation, Neoplastic
MH  - Genetic Vectors
MH  - Humans
MH  - Immunohistochemistry
MH  - Lymphatic Metastasis
MH  - Macrophages/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Microscopy, Fluorescence
MH  - Neoplasm Transplantation
MH  - *Neovascularization, Pathologic
MH  - RNA, Messenger/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Stomach Neoplasms/*genetics/*metabolism/*pathology
MH  - Temperature
MH  - Time Factors
MH  - Transfection
EDAT- 2005/11/10 09:00
MHDA- 2006/04/06 09:00
CRDT- 2005/11/10 09:00
PHST- 2005/11/10 09:00 [pubmed]
PHST- 2006/04/06 09:00 [medline]
PHST- 2005/11/10 09:00 [entrez]
AID - 11/21/7629 [pii]
AID - 10.1158/1078-0432.CCR-05-0798 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2005 Nov 1;11(21):7629-36. doi: 10.1158/1078-0432.CCR-05-0798.