Bone marrow-derived myofibroblasts are the providers of pro-invasive matrix metalloproteinase 13 in primary tumor
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Neoplasia (New York, N.Y.) |
Volume | 14 |
Issue number | 10 |
Pages (from-to) | 943-51 |
Number of pages | 9 |
ISSN | 1522-8002 |
Publication status | Published - Oct 2012 |
- Animals, Blotting, Western, Bone Marrow, Female, Fibroblasts, Flow Cytometry, Humans, Immunoenzyme Techniques, In Situ Hybridization, Matrix Metalloproteinase 13, Mesenchymal Stromal Cells, Mice, Mice, Inbred C57BL, Mice, Transgenic, Myofibroblasts, Neoplasm Invasiveness, Neoplasms, RNA, Messenger, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Tumor Cells, Cultured, Tumor Markers, Biological, Tumor Microenvironment
Research areas
ID: 107123525