Abstract |
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.
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Authors | 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 |
Journal | Neoplasia (New York, N.Y.)
(Neoplasia)
Vol. 14
Issue 10
Pg. 943-51
(Oct 2012)
ISSN: 1476-5586 [Electronic] United States |
PMID | 23097628
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers, Tumor
- RNA, Messenger
- Matrix Metalloproteinase 13
- Mmp13 protein, mouse
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Topics |
- Animals
- Biomarkers, Tumor
(genetics, metabolism)
- Blotting, Western
- Bone Marrow
(metabolism, pathology)
- Female
- Fibroblasts
(metabolism, pathology)
- Flow Cytometry
- Humans
- Immunoenzyme Techniques
- In Situ Hybridization
- Matrix Metalloproteinase 13
(physiology)
- Mesenchymal Stem Cells
(metabolism, pathology)
- Mice
- 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 Microenvironment
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