Document Detail

Bone marrow-derived myofibroblasts are the providers of pro-invasive matrix metalloproteinase 13 in primary tumor.
MedLine Citation:
PMID:  23097628     Owner:  NLM     Status:  MEDLINE    
Carcinoma-associated fibroblasts are key contributors of the tumor microenvironment that regulates carcinoma progression. They consist of a heterogeneous cell population with diverse origins, phenotypes, and functions. In the present report, we have explored the contribution of bone marrow (BM)-derived cells to generate different fibroblast subsets that putatively produce the matrix metalloproteinase 13 (MMP13) and affect cancer cell invasion. A murine model of skin carcinoma was applied to mice, irradiated, and engrafted with BM isolated from green fluorescent protein (GFP) transgenic mice. We provide evidence that one third of BM-derived GFP(+) cells infiltrating the tumor expressed the chondroitin sulfate proteoglycan NG2 (pericytic marker) or α-smooth muscle actin (α-SMA, myofibroblast marker), whereas almost 90% of Thy1(+) fibroblasts were originating from resident GFP-negative cells. MMP13producing cells were exclusively α-SMA(+) cells and derived from GFP(+) BM cells. To investigate their impact on tumor invasion, we isolated mesenchymal stem cells (MSCs) from the BM of wild-type and MMP13-deficient mice. Wild-type MSC promoted cancer cell invasion in a spheroid assay, whereas MSCs obtained from MMP13-deficient mice failed to. Our data support the concept of fibroblast subset specialization with BM-derived α-SMA(+) cells being the main source of MMP13, a stromal mediator of cancer cell invasion.
Julie Lecomte; Anne Masset; Silvia Blacher; Ludovic Maertens; André Gothot; Marie Delgaudine; Françoise Bruyère; Oriane Carnet; Jenny Paupert; Martin Illemann; Jean-Michel Foidart; Ida K Lund; Gunilla Høyer-Hansen; Agnes Noel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neoplasia (New York, N.Y.)     Volume:  14     ISSN:  1476-5586     ISO Abbreviation:  Neoplasia     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-25     Completed Date:  2013-04-04     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  100886622     Medline TA:  Neoplasia     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  943-51     Citation Subset:  IM    
Laboratory of Tumor and Development Biology, GIGA-Cancer, University of Liège, Liège, Belgium.
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MeSH Terms
Blotting, Western
Bone Marrow / metabolism,  pathology*
Fibroblasts / metabolism,  pathology*
Flow Cytometry
Immunoenzyme Techniques
In Situ Hybridization
Matrix Metalloproteinase 13 / physiology*
Mesenchymal Stromal Cells / metabolism,  pathology*
Mice, Inbred C57BL
Mice, Transgenic
Myofibroblasts / metabolism,  pathology*
Neoplasm Invasiveness
Neoplasms / genetics,  metabolism,  pathology*
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
Tumor Markers, Biological / genetics,  metabolism
Tumor Microenvironment
Reg. No./Substance:
0/RNA, Messenger; 0/Tumor Markers, Biological; EC 3.4.24.-/Matrix Metalloproteinase 13; EC 3.4.24.-/Mmp13 protein, mouse

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