Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877

Abstract

Intercellular communication between different cell types in solid tumors contributes to tumor growth and metastatic dissemination. The secretome of cancer-associated fibroblasts (CAFs) plays major roles in these processes. Using human mammary CAFs, we showed that CAFs with a myofibroblast phenotype released extracellular vesicles that transferred proteins to endothelial cells (ECs) that affected their interaction with immune cells. Mass spectrometry–based proteomics identified proteins transferred from CAFs to ECs, which included plasma membrane receptors. Using THY1 as an example of a transferred plasma membrane–bound protein, we showed that CAF-derived proteins increased the adhesion of a monocyte cell line to ECs. CAFs produced high amounts of matrix-bound EVs, which were the primary vehicles of protein transfer. Hence, our work paves the way for future studies that investigate how CAF-derived matrix-bound EVs influence tumor pathology by regulating the function of neighboring cancer, stromal, and immune cells.

People
Santi, Alice
Author

Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877

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Kay, Emily J.
Author

Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877

Neilson, Lisa J. and Cartwright, Douglas and Risteli, Maija and Jokinen, Elina M. and McGarry, Lynn and Sandvik, Toni and Nikolatou, Konstantina and Hodge, Kelly and Atkinson, Samuel and Vias, Maria and Kay, Emily J. and Brenton, James D. and Carlin, Leo M. and Bryant, David M. and Salo, Tuula and Zanivan, Sara (2023) Omentum-derived matrix enables the study of metastatic ovarian cancer and stromal cell functions in a physiologically relevant environment. Matrix Biology Plus, 19-20: 100136. ISSN 2590-0285

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Neilson, Lisa J.
Author

Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877

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McGarry, Lynn
Author

Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877

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Lilla, Sergio
Author

Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877

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Mullin, Margaret
Author

Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877

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Paul, Nikki R.
Author

Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877

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Fercoq, Frederic
Author

Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877

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Koulouras, Grigorios
Author

Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877

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Rodriguez Blanco, Giovanny
Author

Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877

Dawson, Amy and Zarou, Martha M. and Prasad, Bodhayan and Bittencourt-Silvestre, Joana and Zerbst, Désirée and Himonas, Ekaterini and Hsieh, Ya-Ching and van Loon, Isabel and Rodriguez Blanco, Giovanny and Ianniciello, Angela and Kerekes, Zsombor and Krishnan, Vaidehi and Agarwal, Puneet and Almasoudi, Hassan and McCluskey, Laura and Hopcroft, Lisa E.M. and Scott, Mary T. and Baquero, Pablo and Dunn, Karen and Vetrie, David and Copland, Mhairi and Bhatia, Ravi and Coffelt, Seth B. and Tiong, Ong Sin and Wheadon, Helen and Zanivan, Sara and Kirschner, Kristina and Helgason, G. Vignir (2024) Leukaemia exposure alters the transcriptional profile and function of BCR::ABL1 negative macrophages in the bone marrow niche. Nature Communications, 15: 1090. ISSN 2041-1723

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Athineos, Dimitris
Author

Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877

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Mason, Susan
Author

Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877

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Hughes, Mark
Author

Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877

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Thomson, Gemma
Author

Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877

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Kieffer, Yann
Author

Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877

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Nixon, Colin
Author

Pennel, Kathryn A.F. and Hatthakarnkul, Phimmada and Wood, Colin S. and Lian, Guang-Yu and Al-Badran, Sara and Quinn, Jean A. and Legrini, Assya and Inthagard, Jitwadee and Alexander, Peter G. and van Wyk, Hester and Kurniawan, Ahmad and Hashmi, Umar and Gillespie, Michael A. and Mills, Megan and Ammar, Aula and Hay, Jennifer and Andersen, Ditte and Nixon, Colin and Rebus, Selma and Chang, David K. and Kelly, Caroline and Harkin, Andrea and Graham, Janet and Church, David and Tomlinson, Ian and Saunders, Mark and Iveson, Tim and Lannagan, Tamsin R. M. and Jackstadt, Rene and Maka, Noori and Horgan, Paul G. and Roxburgh, Campbell S. D. and Sansom, Owen J. and McMillan, Donald C. and Steele, Colin W. and Jamieson, Nigel B. and Park, James H. and Roseweir, Antonia K. and Edwards, Joanne (2024) JAK/STAT3 represents a therapeutic target for colorectal cancer patients with stromal-rich tumors. Journal of Experimental and Clinical Cancer Research, 43: 64. ISSN 1756-9966

O’Rourke, Colm J. and Salati, Massimiliano and Rae, Colin and Carpino, Guido and Leslie, Holly and Pea, Antonio and Prete, Maria G. and Bonetti, L.R. and Amato, Francesco and Montal, R. and Upstill-Goddard, Rosie and Nixon, Colin and Sanchon-Sanchez, Paula and Kunderfranco, Paolo and Sia, Daniela and Gaudio, Eugenio and Overi, Diletta and Cascinu, Stefano and Hogdall, Dan and Pugh, Sian and Domingo, Enric and Primrose, John N. and Bridgewater, John and Spallanzi, A. and Gelsomino, F. and Llovet, J.M. and Calvisi, Diego F. and Boulter, Luke and Caputo, F. and Lleo, Ana and Jamieson, Nigel B. and Luppi, G. and Dominici, M. and Andersen, Jesper B. and Braconi, Chiara (2024) Molecular portraits of patients with intrahepatic cholangiocarcinoma who diverge as rapid progressors or long survivors on chemotherapy. Gut, 73 (3). pp. 496-508. ISSN 0017-5749

Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877

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Blyth, Karen
Author

Elbassioni, Ali Ali Mohamed and Raheem, Anmar A. and Song, Jian and Johnston, Alexander S. and Trivett, Cara and Lin, Hong and Zhang, Haobo and Bradley, Ashley and Higgins, Erin and Mooney, Leanne and Koay, Yen Chin and O'Toole, Dylan and Herzyk, Pawel and Nixon, Colin and Blyth, Karen and O'Sullivan, John F. and Lang, Ninian N. and Berry, Colin and Braun, Thomas and Schiattarella, Gabriele G. and Giacca, Mauro and McBride, Martin W. and Nicklin, Stuart A. and Cameron, Ewan R. and Loughrey, Christopher M. and MacDonald, Eilidh A. (2025) Targeting Runx1 protects against heart failure with preserved ejection fraction. bioRxiv.

Strathearn, Lauren S. and Spender, Lindsay C. and Schoenherr, Christina and Mason, Susan and Edwards, Ruaridh and Blyth, Karen and Inman, Gareth (2024) C1orf106 (INAVA) is a SMAD3-dependent TGF-β target gene that promotes clonogenicity and correlates with poor prognosis in breast cancer. Cells, 13 (18): 1530. ISSN 2073-4409

Mardilovich, Katerina and Naylor, Gregory and Julian, Linda and Phinichkusolchit, Narisa and Keeshan, Karen and Blyth, Karen and Olson, Michael F. (2024) Caspase-resistant ROCK1 expression prolongs survival of Eµ-Myc B cell lymphoma mice. Disease Models and Mechanisms, 17 (5): dmm050631. ISSN 1754-8403

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Mechta-Grigoriou, Fatima
Author

Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877

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Carlin, Leo M.
Author

Li, Chenxi and Liu, Qiongliang and Han, Lianyong and Zhang, Haiyun and Immler, Roland and Rathkolb, Birgit and Secklehner, Judith and de Angelis, Martin Hrabe and Yildirim, Ali Önder and Zeuschner, Dagmar and Nicke, Annette and Carlin, Leo M. and Sperandio, Markus and Stoeger, Tobias and Rehberg, Markus (2024) The eATP/P2×7R Axis drives quantum dot-nanoparticle induced neutrophil recruitment in the pulmonary microcirculation. Advanced Science, 11 (45): 2404661. ISSN 2198-3844

Xavier, Vanessa and Martinelli, Silvia and Corbyn, Ryan and Pennie, Rachel and Rakovic, Kai and Powley, Ian R. and Officer-Jones, Leah and Ruscica, Vincenzo and Galloway, Alison and Carlin, Leo M. and Cowling, Victoria H. and Le Quesne, John and Martinou, Jean-Claude and MacVicar, Thomas (2024) Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression. Life Science Alliance, 7 (11): e202402764. ISSN 2575-1077

Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877

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Zanivan, Sara
Author

Singh, Shashi P. and Smyth, Danielle J. and Cunningham, Kyle T. and Mukundan, Ananya and Byeon, Chang-Hyeock and Hinck, Cynthia S. and White, Madeleine P.J. and Ciancia, Claire and Wąsowska, Natalia and Sanders, Anna and Jin, Regina and White, Ruby F. and Lilla, Sergio and Zanivan, Sara and Schoenherr, Christina and Inman, Gareth and van Dinther, Maarten and ten Dijke, Peter and Hinck, Andrew P. and Maizels, Rick M. (2025) The TGF-β mimic TGM4 achieves cell specificity through combinatorial surface co-receptor binding. EMBO Reports, 26 (1). pp. 218-244. ISSN 1469-221X

Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877

Vringer, Esmee and Heilig, Rosalie and Riley, Joel S. and Black, Annabel and Cloix, Catherine and Skalka, George and Montes-Gómez, Alfredo E. and Aguado, Aurore and Lilla, Sergio and Walczak, Henning and Gyrd-Hansen, Mads and Murphy, Daniel J. and Huang, Danny T. and Zanivan, Sara and Tait, Stephen W.G. (2024) Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response. EMBO Journal, 43 (6). pp. 904-930. ISSN 0261-4189

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