Linked Life Data

21454378

Source:http://linkedlifedata.com/resource/pubmed/id/21454378

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-5-17
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Ly, http://linkedlifedata.com/resource/pubmed/chemical/Cadherins, http://linkedlifedata.com/resource/pubmed/chemical/Cdh16 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Connective Tissue Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/Ctgf protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Conditioned, http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Matrix Proteins, http://linkedlifedata.com/resource/pubmed/chemical/FBLN5 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Ly6 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 3, http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 9
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1557-3125
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
553-63
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Role of fibulin-5 in metastatic organ colonization.
pubmed:affiliation
Department of Tumor Microenvironment and Metastasis, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't