In this article, the authors explored why cardiac metastases remain rare despite continuous coronary perfusion. In a mouse heterotopic heart transplantation model, lung adenocarcinoma cells showed limited growth in mechanically loaded native hearts but extensively proliferated in unloaded transplanted hearts, replacing much of the myocardium within two weeks. Similar findings were reproduced in engineered beating cardiac tissues, where mechanical loading suppressed proliferation of lung cancer, melanoma, and colon cancer cells. Human cardiac metastases shared a distinct transcriptional profile characterized by the upregulation of histone demethylases and reduced levels of H3K9me3 and chromatin compaction. Mechanistically, the mechanosensor Nesprin-2 translated myocardial load into anti-proliferative chromatin remodeling. Silencing Nesprin-2 restored tumor growth in loaded hearts, suggesting that cardiac mechanical forces may clinically contribute to the heart’s resistance to metastatic cancer.
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Mechanical Load Inhibits Cancer Growth in Mouse and Human Hearts
Submitted by: Vincent Sier
Source: Science
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Author(s): Giulio Ciucci, Daniela Lorizio, Nicoletta Bartoloni, Mauricio Budini, Andrea Colliva, Simone Vodret, Anh-Vu Nguyen, Lorenzo Ciacci, Bernhard Texler, Benno Cardini, Rupert Oberhuber, Sofia Bindelli, Ilaria Luciana Carlotta Del Giudice, Roman Vuerich, Francesco Riccitelli, Elena Zago, Henrik Nicolay Finsberg, Mattia Chiesa, Gianluca Lorenzo Perrucci, Rossana Bussani, Furio Silvestri, Manuel Maglione, Gaetano Ivan Dellino, Gianfranco Sinagra, Mauro Giacca, Thomas Eschenhagen, Paolo Golino, Giulio Pompilio, Pier Giuseppe Pelicci, Laura Andolfi, Maurizio Pinamonti, Matteo Dal Ferro, Samuel Wall, Francesco S. Loffredo, Serena Zacchigna
