Tumor Biomechanics Alters Metastatic Dissemination of Triple Negative Breast Cancer via Rewiring Fatty Acid Metabolism.

Autor: Filipe EC; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.; School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia., Velayuthar S; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia., Philp A; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.; School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.; Centenary Institute, Camperdown, NSW, 2050, Australia., Nobis M; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.; School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia., Latham SL; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.; School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia., Parker AL; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.; School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia., Murphy KJ; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.; School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia., Wyllie K; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.; School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia., Major GS; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia., Contreras O; School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, 2010, Australia., Mok ETY; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.; School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia., Enriquez RF; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia., McGowan S; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia., Feher K; South Australian immunoGENomics Cancer Institute (SAiGENCI), Adelaide, SA, 5005, Australia., Quek LE; School of Mathematics and Statistics, Charles Perkins Centre, University of Sydney, Sydney, 2050, Australia., Hancock SE; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, 2010, Australia.; School of Biomedical Sciences, UNSW Sydney, Sydney, 2033, Australia., Yam M; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia., Tran E; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia., Setargew YFI; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia., Skhinas JN; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia., Chitty JL; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.; School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia., Phimmachanh M; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia., Han JZR; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia., Cadell AL; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia., Papanicolaou M; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.; School of Life Sciences, University of Technology Sydney, Sydney, NSW, 2007, Australia., Mahmodi H; School of Mathematical and Physical Sciences, University of Technology Sydney, Sydney, NSW, 2007, Australia., Kiedik B; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia., Junankar S; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.; School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia., Ross SE; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia., Lam N; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia., Coulson R; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia., Yang J; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia., Zaratzian A; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia., Da Silva AM; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia., Tayao M; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia., Chin IL; School of Human Sciences, University of Western Australia, Crawley, WA, 6009, Australia., Cazet A; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.; School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia., Kansara M; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.; School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia., Segara D; St Vincent's Hospital, Darlinghurst, NSW, 2010, Australia., Parker A; School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.; Department of Pathology, St. Vincent's Hospital, Sydney, 2010, Australia., Hoy AJ; School of Medical Sciences, Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, 2050, Australia., Harvey RP; School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, 2010, Australia., Bogdanovic O; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.; School of Biotechnology and Biomolecular Sciences, UNSW Sydney, Sydney, 2033, Australia., Timpson P; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.; School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia., Croucher DR; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.; School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia., Lim E; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.; School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia., Swarbrick A; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.; School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia., Holst J; School of Biomedical Sciences, UNSW Sydney, Sydney, 2033, Australia., Turner N; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, 2010, Australia.; School of Biomedical Sciences, UNSW Sydney, Sydney, 2033, Australia., Choi YS; School of Human Sciences, University of Western Australia, Crawley, WA, 6009, Australia., Kabakova IV; School of Mathematical and Physical Sciences, University of Technology Sydney, Sydney, NSW, 2007, Australia., Philp A; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.; School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.; Biology of Ageing Laboratory and Centre for Healthy Ageing, Centenary Institute, Missenden Road, Camperdown, Sydney, NSW, 2050, Australia.; School of Sport, Exercise and Rehabilitation Sciences, University of Technology Sydney, Ultimo, NSW, 2007, Australia., Cox TR; Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.; School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Jun; Vol. 11 (23), pp. e2307963. Date of Electronic Publication: 2024 Apr 11.
DOI: 10.1002/advs.202307963
Abstrakt: In recent decades, the role of tumor biomechanics on cancer cell behavior at the primary site has been increasingly appreciated. However, the effect of primary tumor biomechanics on the latter stages of the metastatic cascade, such as metastatic seeding of secondary sites and outgrowth remains underappreciated. This work sought to address this in the context of triple negative breast cancer (TNBC), a cancer type known to aggressively disseminate at all stages of disease progression. Using mechanically tuneable model systems, mimicking the range of stiffness's typically found within breast tumors, it is found that, contrary to expectations, cancer cells exposed to softer microenvironments are more able to colonize secondary tissues. It is shown that heightened cell survival is driven by enhanced metabolism of fatty acids within TNBC cells exposed to softer microenvironments. It is demonstrated that uncoupling cellular mechanosensing through integrin β1 blocking antibody effectively causes stiff primed TNBC cells to behave like their soft counterparts, both in vitro and in vivo. This work is the first to show that softer tumor microenvironments may be contributing to changes in disease outcome by imprinting on TNBC cells a greater metabolic flexibility and conferring discrete cell survival advantages.
(© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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