Shimrit Avraham1, Soraya Abu-Sharki1, Rona Shofti2, Tali Haas2, Ben Korin3, Roy Kalfon1, Tom Friedman4, Avinoam Shiran5, Walid Saliba6, Yuval Shaked1, Ami Aronheim1. 1. Department of Cell Biology and Cancer Science, The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa Israel. 2. The Pre-Clinical Research Authority Unit, Technion - Israel Institute of Technology, Haifa Israel. 3. Department of Immunology, The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa Israel; Department of Neuroscience, The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa Israel. 4. Department of Cell Biology and Cancer Science, The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa Israel; Department of Cardiac Surgery, Rambam Medical Center, Haifa, Israel. 5. Department of Cardiovascular Medicine, Lady Davis Carmel Medical Center and The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa Israel. 6. Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center and The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa Israel.
Abstract
Background: Recent evidence suggests that cancer and cardiovascular diseases are associated. Chemotherapy drugs are known to result in cardiotoxicity, and studies have shown that heart failure (HF) and stress correlate with poor cancer prognosis. Yet, whether cardiac remodeling in the absence of HF is sufficient to promote cancer is unknown. Methods: To investigate the effect of early cardiac remodeling on tumor growth and metastasis colonization, we used transverse aortic constriction (TAC), a model for pressure overload-induced cardiac hypertrophy, and followed it by cancer cell implantation. Results: TAC-operated mice developed larger primary tumors with higher proliferation rate and displayed more metastatic lesions compared with controls. Serum derived from TAC-operated mice potentiated cancer cell proliferation in vitro, suggesting the existence of secreted tumor-promoting factors. Using RNA-seq data, we identified elevated mRNA levels of Periostin in the hearts of TAC-operated mice. Periostin levels were also found high in the serum following TAC. Interestingly, depletion of Periostin from the serum abrogated the proliferation of cancer cells, conversely, the addition of Periostin enhanced cancer cell proliferation in vitro. Collectively, this is the first study to show that early cardiac remodeling nurtures tumor growth and metastasis, and therefore promotes cancer progression. Conclusions: Our study highlights the importance of early diagnosis and treatment of cardiac remodeling as it may attenuate cancer progression and improve cancer outcome.
Background: Recent evidence suggests that cancer and cardiovascular diseases are associated. Chemotherapy drugs are known to result in cardiotoxicity, and studies have shown that heart failure (HF) and stress correlate with poor cancer prognosis. Yet, whether cardiac remodeling in the absence of HF is sufficient to promote cancer is unknown. Methods: To investigate the effect of early cardiac remodeling on tumor growth and metastasis colonization, we used transverse aortic constriction (TAC), a model for pressure overload-induced cardiac hypertrophy, and followed it by cancer cell implantation. Results:TAC-operated mice developed larger primary tumors with higher proliferation rate and displayed more metastatic lesions compared with controls. Serum derived from TAC-operated mice potentiated cancer cell proliferation in vitro, suggesting the existence of secreted tumor-promoting factors. Using RNA-seq data, we identified elevated mRNA levels of Periostin in the hearts of TAC-operated mice. Periostin levels were also found high in the serum following TAC. Interestingly, depletion of Periostin from the serum abrogated the proliferation of cancer cells, conversely, the addition of Periostin enhanced cancer cell proliferation in vitro. Collectively, this is the first study to show that early cardiac remodeling nurtures tumor growth and metastasis, and therefore promotes cancer progression. Conclusions: Our study highlights the importance of early diagnosis and treatment of cardiac remodeling as it may attenuate cancer progression and improve cancer outcome.
Entities:
Keywords:
Periostin; cancer and stroke; transverse aortic constriction
Authors: Graeme J Koelwyn; Joseph Pierre Aboumsallem; Kathryn J Moore; Rudolf A de Boer Journal: J Mol Cell Cardiol Date: 2021-09-25 Impact factor: 5.000
Authors: Petr Kala; Hana Bartušková; Jan Piťha; Zdenka Vaňourková; Soňa Kikerlová; Šárka Jíchová; Vojtěch Melenovský; Lenka Hošková; Josef Veselka; Elzbieta Kompanowska-Jezierska; Janusz Sadowski; Olga Gawrys; Hana Maxová; Luděk Červenka Journal: Int J Mol Sci Date: 2020-12-08 Impact factor: 5.923
Authors: Rudolf A de Boer; Jean-Sébastien Hulot; Carlo Gabriele Tocchetti; Joseph Pierre Aboumsallem; Pietro Ameri; Stefan D Anker; Johann Bauersachs; Edoardo Bertero; Andrew J S Coats; Jelena Čelutkienė; Ovidiu Chioncel; Pierre Dodion; Thomas Eschenhagen; Dimitrios Farmakis; Antoni Bayes-Genis; Dirk Jäger; Ewa A Jankowska; Richard N Kitsis; Suma H Konety; James Larkin; Lorenz Lehmann; Daniel J Lenihan; Christoph Maack; Javid J Moslehi; Oliver J Müller; Patrycja Nowak-Sliwinska; Massimo Francesco Piepoli; Piotr Ponikowski; Radek Pudil; Peter P Rainer; Frank Ruschitzka; Douglas Sawyer; Petar M Seferovic; Thomas Suter; Thomas Thum; Peter van der Meer; Linda W Van Laake; Stephan von Haehling; Stephane Heymans; Alexander R Lyon; Johannes Backs Journal: Eur J Heart Fail Date: 2020-11-12 Impact factor: 15.534
Authors: Rudolf A de Boer; Joseph Pierre Aboumsallem; Valentina Bracun; Douglas Leedy; Richard Cheng; Sahishnu Patel; David Rayan; Svetlana Zaharova; Jennifer Rymer; Jennifer M Kwan; Joshua Levenson; Claudio Ronco; Paaladinesh Thavendiranathan; Sherry-Ann Brown Journal: Cardiooncology Date: 2021-06-21