PMID- 19479998
OWN - NLM
STAT- MEDLINE
DCOM- 20090820
LR  - 20220309
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 125
IP  - 6
DP  - 2009 Sep 15
TI  - Stromal MCP-1 in mammary tumors induces tumor-associated macrophage infiltration 
      and contributes to tumor progression.
PG  - 1276-84
LID - 10.1002/ijc.24378 [doi]
AB  - There is growing evidence that tumor-associated macrophages (TAMs) promote tumor 
      growth and dissemination. Many individual reports have focused on the protumor 
      function of molecules linked to the recruitment of macrophages, but little is 
      known about which factor has the strongest impact on recruitment of macrophages 
      in breast cancer. To elucidate this question, we performed RT-PCR using 
      species-specific primers and evaluated tumoral and stromal mRNA expression of 
      macrophage chemoattractants separately in human breast tumor xenografts. The 
      correlation between the tumoral or stromal chemoattractant mRNA expression 
      including monocyte chemoattractant protein-1 (MCP-1) (CCL2), MIP-1alpha (CCL3), 
      RANTES (CCL5), colony-stimulating factor 1, tumor necrosis factor alpha, 
      platelet-derived growth factor (PDGF)-BB and macrophage infiltration were 
      compared. There was significant positive correlation between stromal MCP-1 
      expression and macrophage number (r = 0.63), and negative correlation between 
      tumoral RANTES expression and macrophage number (r = -0.75). However, no 
      significant correlation was found for the other tumoral and stromal factors. The 
      interaction between the tumor cells and macrophages was also investigated. Tumor 
      cell-macrophage interactions augmented macrophage-derived MCP-1 mRNA expression 
      and macrophage chemotactic activity in vitro. Treatment of immunodeficient mice 
      bearing human breast cancer cells with a neutralizing antibody to MCP-1 resulted 
      in significant decrease of macrophage infiltration, angiogenetic activity and 
      tumor growth. Furthermore, immunohistochemical analysis of human breast cancer 
      tissue showed stromal MCP-1 had a significant correlation with relapse free 
      survival (p = 0.029), but tumoral MCP-1 did not (p = 0.105). These findings 
      indicate that stromal MCP-1 produced as a result of tumor-stromal interactions 
      may be important for the progression of human breast cancer and macrophages may 
      play an important role in this tumor-stroma interaction.
CI  - 2009 UICC
FAU - Fujimoto, Hiroshi
AU  - Fujimoto H
AD  - Pathology Division, Research Center for Innovative Oncology, National Cancer 
      Center Hospital East, Kashiwa-City, Chiba, Japan.
FAU - Sangai, Takafumi
AU  - Sangai T
FAU - Ishii, Genichiro
AU  - Ishii G
FAU - Ikehara, Akashi
AU  - Ikehara A
FAU - Nagashima, Takeshi
AU  - Nagashima T
FAU - Miyazaki, Masaru
AU  - Miyazaki M
FAU - Ochiai, Atsushi
AU  - Ochiai A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL3)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Proto-Oncogene Proteins c-sis)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1B56C968OA (Becaplermin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Becaplermin
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Breast Neoplasms/*metabolism/*physiopathology
MH  - Chemokine CCL2/*physiology
MH  - Chemokine CCL3/genetics/metabolism
MH  - Chemokine CCL5/genetics/metabolism
MH  - Chemotaxis
MH  - Culture Media, Conditioned
MH  - Disease Progression
MH  - Female
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Macrophages, Peritoneal/*physiology
MH  - Mice
MH  - Mice, SCID
MH  - Microscopy, Confocal
MH  - Middle Aged
MH  - Platelet-Derived Growth Factor/genetics/metabolism
MH  - Prognosis
MH  - Proto-Oncogene Proteins c-sis
MH  - RNA, Messenger/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Stromal Cells/*metabolism
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
EDAT- 2009/05/30 09:00
MHDA- 2009/08/21 09:00
CRDT- 2009/05/30 09:00
PHST- 2009/05/30 09:00 [entrez]
PHST- 2009/05/30 09:00 [pubmed]
PHST- 2009/08/21 09:00 [medline]
AID - 10.1002/ijc.24378 [doi]
PST - ppublish
SO  - Int J Cancer. 2009 Sep 15;125(6):1276-84. doi: 10.1002/ijc.24378.