PMID- 21454378
OWN - NLM
STAT- MEDLINE
DCOM- 20110830
LR  - 20211020
IS  - 1557-3125 (Electronic)
IS  - 1541-7786 (Linking)
VI  - 9
IP  - 5
DP  - 2011 May
TI  - Role of fibulin-5 in metastatic organ colonization.
PG  - 553-63
LID - 10.1158/1541-7786.MCR-11-0093 [doi]
AB  - The tumor microenvironment is now recognized as a major factor in determining the 
      survival and growth of disseminated tumor cells at potential metastatic sites. 
      Tumor cells send signals to stroma cells and stimulate them to produce factors 
      that in turn create favorable conditions for tumor cell metastasis. Activated 
      fibroblasts constitute an important component of the tumor-associated stroma. We 
      have previously shown that S100A4 protein produced by stromal fibroblasts in the 
      primary tumor stimulates metastasis formation. Here we show that activated 
      fibroblasts also stimulate the formation of metastases independently of S100A4 
      expression during organ colonization. To identify genes that could potentially 
      interfere with fibroblast-driven metastasis, we used gene expression profiling of 
      S100A4-deficient fibroblasts treated with and without tumor cell-conditioned 
      media. Five differentially expressed genes encoding cell surface and secreted 
      proteins with potential metastasis-modulating activity were selected. Expression 
      of lymphocyte antigen 6 complex (Ly6c) and matrix metalloproteinase 3 (Mmp3) was 
      upregulated in fibroblasts in response to tumor-conditioned medium, whereas 
      expression of cadherin-16 (Cdh16), Ccn2, and fibulin-5 (Fbln5) was downregulated. 
      Further analysis showed that Fibulin-5 is able to suppress the metastatic 
      colonization of lungs and liver. Additional studies suggest a mechanism in which 
      Fibulin-5 suppresses metastasis formation by inhibiting production of matrix 
      metalloproteinase 9 (MMP9) and reducing the invasive behavior of fibroblasts. 
      Together our data are consistent with the notion that tumors secrete factors that 
      downregulate expression of Fbln5 in fibroblasts at sites of metastatic 
      colonization, in turn upregulating Mmp9 expression and stimulating metastatic 
      organ colonization.
FAU - Moller, Henrik Devitt
AU  - Moller HD
AD  - Department of Tumor Microenvironment and Metastasis, Danish Cancer Society, 
      Strandboulevarden 49, DK-2100 Copenhagen, Denmark.
FAU - Ralfkjaer, Ulrik
AU  - Ralfkjaer U
FAU - Cremers, Natascha
AU  - Cremers N
FAU - Frankel, Mika
AU  - Frankel M
FAU - Pedersen, Rune Troelsgaard
AU  - Pedersen RT
FAU - Klingelhofer, Jorg
AU  - Klingelhofer J
FAU - Yanagisawa, Hiromi
AU  - Yanagisawa H
FAU - Grigorian, Mariam
AU  - Grigorian M
FAU - Guldberg, Per
AU  - Guldberg P
FAU - Sleeman, Jonathan
AU  - Sleeman J
FAU - Lukanidin, Eugene
AU  - Lukanidin E
FAU - Ambartsumian, Noona
AU  - Ambartsumian N
LA  - eng
GR  - R01 HD064824/HD/NICHD NIH HHS/United States
GR  - R01 HL106305/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110331
PL  - United States
TA  - Mol Cancer Res
JT  - Molecular cancer research : MCR
JID - 101150042
RN  - 0 (Antigens, Ly)
RN  - 0 (CCN2 protein, mouse)
RN  - 0 (Cadherins)
RN  - 0 (Cdh16 protein, mouse)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (FBLN5 protein, human)
RN  - 0 (Ly6 protein, mouse)
RN  - 139568-91-5 (Connective Tissue Growth Factor)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Antigens, Ly/drug effects/metabolism
MH  - Cadherins/drug effects/metabolism
MH  - Cell Line, Tumor
MH  - Connective Tissue Growth Factor/drug effects/metabolism
MH  - Culture Media, Conditioned/pharmacology
MH  - Down-Regulation
MH  - Extracellular Matrix Proteins/drug effects/*metabolism
MH  - Fibroblasts/drug effects/*metabolism
MH  - *Gene Expression Regulation, Neoplastic
MH  - Liver Neoplasms/genetics/*secondary
MH  - Lung Neoplasms/genetics/*secondary
MH  - Matrix Metalloproteinase 3/drug effects/metabolism
MH  - Matrix Metalloproteinase 9/drug effects/*metabolism
MH  - Mice
EDAT- 2011/04/02 06:00
MHDA- 2011/08/31 06:00
CRDT- 2011/04/02 06:00
PHST- 2011/04/02 06:00 [entrez]
PHST- 2011/04/02 06:00 [pubmed]
PHST- 2011/08/31 06:00 [medline]
AID - 1541-7786.MCR-11-0093 [pii]
AID - 10.1158/1541-7786.MCR-11-0093 [doi]
PST - ppublish
SO  - Mol Cancer Res. 2011 May;9(5):553-63. doi: 10.1158/1541-7786.MCR-11-0093. Epub 
      2011 Mar 31.