PMID- 26297433 OWN - NLM STAT- MEDLINE DCOM- 20160609 LR - 20181202 IS - 1476-5586 (Electronic) IS - 1522-8002 (Print) IS - 1476-5586 (Linking) VI - 17 IP - 7 DP - 2015 Jul TI - Mesenchymal Stem Cells Shed Amphiregulin at the Surface of Lung Carcinoma Cells in a Juxtacrine Manner. PG - 552-63 LID - S1476-5586(15)00083-4 [pii] LID - 10.1016/j.neo.2015.07.002 [doi] AB - 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-alpha-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-alpha-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. CI - Copyright (c) 2015 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Carnet, Oriane AU - Carnet O AD - Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liege, B-4000 Liege, Belgium. FAU - Lecomte, Julie AU - Lecomte J AD - Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liege, B-4000 Liege, Belgium. FAU - Masset, Anne AU - Masset A AD - Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liege, B-4000 Liege, Belgium. FAU - Primac, Irina AU - Primac I AD - Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liege, B-4000 Liege, Belgium. FAU - Durre, Tania AU - Durre T AD - Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liege, B-4000 Liege, Belgium. FAU - Maertens, Ludovic AU - Maertens L AD - Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liege, B-4000 Liege, Belgium. FAU - Detry, Benoit AU - Detry B AD - Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liege, B-4000 Liege, Belgium. FAU - Blacher, Silvia AU - Blacher S AD - Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liege, B-4000 Liege, Belgium. FAU - Gilles, Christine AU - Gilles C AD - Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liege, B-4000 Liege, Belgium. FAU - Pequeux, Christel AU - Pequeux C AD - Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liege, B-4000 Liege, Belgium. FAU - Paupert, Jenny AU - Paupert J AD - Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liege, B-4000 Liege, Belgium. FAU - Foidart, Jean-Michel AU - Foidart JM AD - Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liege, B-4000 Liege, Belgium. FAU - Jerusalem, Guy AU - Jerusalem G AD - Department of Medical Oncology, Centre Hospitalier Universitaire (CHU), Sart Tilman, B-4000 Liege, Belgium. FAU - Cataldo, Didier AU - Cataldo D AD - Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liege, B-4000 Liege, Belgium. FAU - Noel, Agnes AU - Noel A AD - Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liege, B-4000 Liege, Belgium. Electronic address: Agnes.Noel@ulg.ac.be. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Neoplasia JT - Neoplasia (New York, N.Y.) JID - 100886622 RN - 0 (Amphiregulin) RN - EC 3.4.24.- (ADAM Proteins) RN - EC 3.4.24.86 (ADAM17 Protein) SB - IM MH - ADAM Proteins/antagonists & inhibitors/metabolism MH - ADAM17 Protein MH - Amphiregulin/*metabolism MH - Animals MH - Bone Marrow Cells/*metabolism MH - Carcinoma, Lewis Lung/*pathology MH - Cell Communication/*physiology MH - Cell Membrane/metabolism MH - Cell Proliferation MH - Female MH - Fluorescence Resonance Energy Transfer MH - Image Processing, Computer-Assisted MH - Mesenchymal Stem Cells/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Neoplasm Invasiveness/pathology MH - Neoplasm Metastasis/pathology MH - Neoplasm Transplantation MH - Spheroids, Cellular MH - Tumor Cells, Cultured PMC - PMC4547406 EDAT- 2015/08/25 06:00 MHDA- 2016/06/10 06:00 PMCR- 2015/08/18 CRDT- 2015/08/23 06:00 PHST- 2015/03/23 00:00 [received] PHST- 2015/06/23 00:00 [revised] PHST- 2015/07/02 00:00 [accepted] PHST- 2015/08/23 06:00 [entrez] PHST- 2015/08/25 06:00 [pubmed] PHST- 2016/06/10 06:00 [medline] PHST- 2015/08/18 00:00 [pmc-release] AID - S1476-5586(15)00083-4 [pii] AID - 10.1016/j.neo.2015.07.002 [doi] PST - ppublish SO - Neoplasia. 2015 Jul;17(7):552-63. doi: 10.1016/j.neo.2015.07.002.