Forskning ved Københavns Universitet - Københavns Universitet


Bone marrow-derived myofibroblasts are the providers of pro-invasive matrix metalloproteinase 13 in primary tumor

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • 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
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.
TidsskriftNeoplasia (New York, N.Y.)
Udgave nummer10
Sider (fra-til)943-51
Antal sider9
StatusUdgivet - okt. 2012

ID: 107123525