Bone Marrow-derived Myofibroblasts Are the Providers of Pro-invasive Matrix Metalloproteinase 13 in Primary Tumor

Autor: 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
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: Neoplasia: An International Journal for Oncology Research, Vol 14, Iss 10, Pp 943-951 (2012)
Druh dokumentu: article
ISSN: 1476-5586
DOI: 10.1593/neo.121092
Popis: 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.
Databáze: Directory of Open Access Journals