Bone marrow-derived myofibroblasts are the providers of pro-invasive matrix metalloproteinase 13 in primary tumor.
Neoplasia
; 14(10): 943-51, 2012 Oct.
Article
em En
| MEDLINE
| ID: mdl-23097628
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Medula Óssea
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Metaloproteinase 13 da Matriz
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Miofibroblastos
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Células-Tronco Mesenquimais
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Fibroblastos
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Neoplasias
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article