Extracellular vesicles from the infarcted and failing heart drive tumor growth
| Autor: | T Caller, O Shaihov Teper, Y Schary, D Lendengolts, I Rotem, R Peled, U Amit, R Shai, E Glick Saar, D Dominissini, A Boomgarden, C D'Souza-Schorey, N Naftali-Shani, J Leor |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | European Heart Journal. 43 |
| ISSN: | 1522-9645 0195-668X |
| Popis: | Aims Heart disease might be an independent risk factor for cancer (reverse cardio-oncology). The co-occurrence of these diseases worsens patients' prognoses and limits therapeutic options. However, the cellular and molecular mechanisms that link heart disease to cancer remain elusive. Therefore, we hypothesized that cardiac extracellular vesicles (cEVs) secreted by diseased hearts carry and disseminate factors that promote tumor growth. Methods and results We subjected female mice to myocardial infarction (MI) or sham-MI and 28 days of follow-up. Left ventricular remodeling and dysfunction were assessed by echocardiography. To determine the role of cEVs in tumor growth, we focused on cardiac mesenchymal stromal cells (cMSCs), which play a central role in cardiac repair, remodeling, and fibrosis. We isolated cMSCs from mice hearts 10 or 28 days after MI or sham MI and purified cMSC-EVs from the conditioned medium using size exclusion chromatography. cEVs were characterized by nanoparticle tracking analysis (NTA), the classical EV markers: CD81 and Tumor susceptibility gene 101, and electron microscopy. cMSCs after MI secreted more small EVs than cMSCs from sham-MI (Fig. 1A, p Conclusions Our results suggest, for the first time, that cMSCs from the infarcted and failing heart secret EVs that target tumor cells and accelerate tumor growth. We propose cEVs as potential mediators and therapeutic targets in patients with concomitant heart disease and cancer. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Seymour Fefer Grant |
| Databáze: | OpenAIRE |
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