PMID- 21989163
OWN - NLM
STAT- MEDLINE
DCOM- 20120417
LR  - 20220321
IS  - 1555-8576 (Electronic)
IS  - 1538-4047 (Print)
IS  - 1538-4047 (Linking)
VI  - 12
IP  - 10
DP  - 2011 Nov 15
TI  - Knockdown of VEGF receptor-1 (VEGFR-1) impairs macrophage infiltration, 
      angiogenesis and growth of clear cell renal cell carcinoma (CRCC).
PG  - 872-80
LID - 10.4161/cbt.12.10.17672 [doi]
AB  - Angiogenesis is essential for tumor growth and metastasis. VEGF has been shown to 
      be a central player in this process. The biological activity of VEGF is mainly 
      mediated by two tyrosine kinase receptors, VEGFR-1 and VEGFR-2. While increasing 
      evidence suggests that VEGF/VEGFR-1 signaling is crucial for tumor angiogenesis, 
      its molecular mechanism is not well understood. Here we show that VEGFR-1 
      knockdown dramatically inhibits tumor growth. This inhibition is associated with 
      significant decrease of tumor VEGF levels and tumor angiogenesis as well as an 
      increased tumor necrosis. Moreover, we demonstrate that VEGF in CRCC tumors is 
      mainly produced by tumor stromal cells instead of the tumor cells themselves. It 
      has been shown that macrophages constitute a significant part of tumor stromal 
      cells and produce a large amount of VEGF. We therefore examined the macrophage 
      infiltration in the xenograft tumors. Remarkably, VEGFR-1 knockdown attenuates 
      the tumor macrophages infiltration. To understand the mechanism, we investigated 
      the impact of VEGFR-1 knockdown on the expression of monocyte chemoattractant 
      protein-1 (MCP-1), one of the main chemoattractants for macrophages. 
      Significantly, VEGFR-1 knockdown inhibits MCP-1 expression of CRCC cells. Taken 
      together, these data indicate that VEGF/VEGFR-1 signaling plays an essential role 
      in initiating tumor angiogenesis by regulating MCP-1 expression, which in turn, 
      attracts macrophages infiltration and VEGF production. Thus, these studies 
      suggest that blockade of VEGFR-1 function may provide a tumor-specific, 
      VEGF-based therapeutic strategy for treatment of CRCC.
FAU - Li, Chenghai
AU  - Li C
AD  - Internal Medicine, Texas Tech University Health Sciences Center, Amarillo, TX, 
      USA.
FAU - Liu, Bin
AU  - Liu B
FAU - Dai, Zonghan
AU  - Dai Z
FAU - Tao, Yunxia
AU  - Tao Y
LA  - eng
GR  - K01 DK067191/DK/NIDDK NIH HHS/United States
GR  - R21 CA133597/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20111115
PL  - United States
TA  - Cancer Biol Ther
JT  - Cancer biology & therapy
JID - 101137842
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Carcinoma, Renal Cell/blood supply/metabolism/*therapy
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Chemokine CCL2/metabolism
MH  - Female
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Kidney Neoplasms/blood supply/metabolism/*therapy
MH  - Macrophages/*physiology
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mice
MH  - Mice, Nude
MH  - Neovascularization, Pathologic/genetics/*therapy
MH  - RNA, Small Interfering/metabolism
MH  - Signal Transduction
MH  - Vascular Endothelial Growth Factor Receptor-1/*antagonists & inhibitors/genetics
MH  - Vascular Endothelial Growth Factors/metabolism
MH  - Xenograft Model Antitumor Assays
PMC - PMC3280902
EDAT- 2011/10/13 06:00
MHDA- 2012/04/18 06:00
PMCR- 2012/11/15
CRDT- 2011/10/13 06:00
PHST- 2011/10/13 06:00 [entrez]
PHST- 2011/10/13 06:00 [pubmed]
PHST- 2012/04/18 06:00 [medline]
PHST- 2012/11/15 00:00 [pmc-release]
AID - 17672 [pii]
AID - 2011CBT4862R [pii]
AID - 10.4161/cbt.12.10.17672 [doi]
PST - ppublish
SO  - Cancer Biol Ther. 2011 Nov 15;12(10):872-80. doi: 10.4161/cbt.12.10.17672. Epub 
      2011 Nov 15.