title: Mesenchymal Stem Cells Shed Amphiregulin at the Surface of Lung Carcinoma Cells in a Juxtacrine Manner.
abstract: Solid tumors comprise cancer cells and different supportive stromal cells, including mesenchymal stem cells (MSCs), which have recently been shown to enhance tumor growth and metastasis. We provide new mechanistic insights into how bone marrow (BM)-derived MSCs co-injected with Lewis lung carcinoma cells promote tumor growth and metastasis in mice. The proinvasive effect of BM-MSCs exerted on tumor cells relies on an unprecedented juxtacrine action of BM-MSC, leading to the trans-shedding of amphiregulin (AREG) from the tumor cell membrane by tumor necrosis factor-α-converting enzyme carried by the BM-MSC plasma membrane. The released soluble AREG activates cancer cells and promotes their invasiveness. This novel concept is supported by the exploitation of different 2D and 3D culture systems and by pharmacological approaches using a tumor necrosis factor-α-converting enzyme inhibitor and AREG-blocking antibodies. Altogether, we here assign a new function to BM-MSC in tumor progression and establish an uncovered link between AREG and BM-MSC.
authors: Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liège, B-4000 Liège, Belgium.
authors: Oriane
authors: O
authors: Carnet
authors: Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liège, B-4000 Liège, Belgium.
authors: Julie
authors: J
authors: Lecomte
authors: Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liège, B-4000 Liège, Belgium.
authors: Anne
authors: A
authors: Masset
authors: Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liège, B-4000 Liège, Belgium.
authors: Irina
authors: I
authors: Primac
authors: Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liège, B-4000 Liège, Belgium.
authors: Tania
authors: T
authors: Durré
authors: Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liège, B-4000 Liège, Belgium.
authors: Ludovic
authors: L
authors: Maertens
authors: Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liège, B-4000 Liège, Belgium.
authors: Benoit
authors: B
authors: Detry
authors: Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liège, B-4000 Liège, Belgium.
authors: Silvia
authors: S
authors: Blacher
authors: Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liège, B-4000 Liège, Belgium.
authors: Christine
authors: C
authors: Gilles
authors: Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liège, B-4000 Liège, Belgium.
authors: Christel
authors: C
authors: Péqueux
authors: Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liège, B-4000 Liège, Belgium.
authors: Jenny
authors: J
authors: Paupert
authors: Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liège, B-4000 Liège, Belgium.
authors: Jean-Michel
authors: JM
authors: Foidart
authors: Department of Medical Oncology, Centre Hospitalier Universitaire (CHU), Sart Tilman, B-4000 Liège, Belgium.
authors: Guy
authors: G
authors: Jerusalem
authors: Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liège, B-4000 Liège, Belgium.
authors: Didier
authors: D
authors: Cataldo
authors: Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liège, B-4000 Liège, Belgium. Electronic address: Agnes.Noel@ulg.ac.be.
authors: Agnès
authors: A
authors: Noel
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000072198:ADAM17 Protein; D066258:Amphiregulin / Q000378:metabolism*; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D018827:Carcinoma, Lewis Lung / Q000473:pathology*; D002450:Cell Communication / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D031541:Fluorescence Resonance Energy Transfer; D007091:Image Processing, Computer-Assisted; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology; D009368:Neoplasm Transplantation; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured
chemical_list: D066258:Amphiregulin; D051722:ADAM Proteins; D000072198:ADAM17 Protein