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

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

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

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

26 Citations (Scopus)

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.

Original language	English
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

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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

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.",

keywords = "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",

author = "Julie Lecomte and Anne Masset and Silvia Blacher and Ludovic Maertens and Andr{\'e} Gothot and Marie Delgaudine and Fran{\c c}oise Bruy{\`e}re and Oriane Carnet and Jenny Paupert and Martin Illemann and Jean-Michel Foidart and Lund, {Ida K} and Gunilla H{\o}yer-Hansen and Agnes Noel",

year = "2012",

month = oct,

language = "English",

volume = "14",

pages = "943--51",

journal = "Neoplasia (United States)",

issn = "1522-8002",

publisher = "Neoplasia Press",

number = "10",

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TY - JOUR

T1 - Bone marrow-derived myofibroblasts are the providers of pro-invasive matrix metalloproteinase 13 in primary tumor

AU - Lecomte, Julie

AU - Masset, Anne

AU - Blacher, Silvia

AU - Maertens, Ludovic

AU - Gothot, André

AU - Delgaudine, Marie

AU - Bruyère, Françoise

AU - Carnet, Oriane

AU - Paupert, Jenny

AU - Illemann, Martin

AU - Foidart, Jean-Michel

AU - Lund, Ida K

AU - Høyer-Hansen, Gunilla

AU - Noel, Agnes

PY - 2012/10

Y1 - 2012/10

N2 - 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.

AB - 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.

KW - Animals

KW - Blotting, Western

KW - Bone Marrow

KW - Female

KW - Fibroblasts

KW - Flow Cytometry

KW - Humans

KW - Immunoenzyme Techniques

KW - In Situ Hybridization

KW - Matrix Metalloproteinase 13

KW - Mesenchymal Stromal Cells

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Myofibroblasts

KW - Neoplasm Invasiveness

KW - Neoplasms

KW - RNA, Messenger

KW - Real-Time Polymerase Chain Reaction

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Tumor Cells, Cultured

KW - Tumor Markers, Biological

KW - Tumor Microenvironment

M3 - Journal article

C2 - 23097628

SN - 1522-8002

VL - 14

SP - 943

EP - 951

JO - Neoplasia (United States)

JF - Neoplasia (United States)

IS - 10

ER -

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

Abstract

Keywords

UN SDGs

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