ABSTRACT
[This corrects the article DOI: 10.1007/s40610-017-0072-8.].
ABSTRACT
PURPOSE OF REVIEW: Store-operated calcium entry (SOCE) is dysregulated in prostate cancer, contributing to increased cellular migration and proliferation and preventing cancer cell apoptosis. We here summarize findings on gene expression levels and functions of SOCE components, stromal interaction molecules (STIM1 and STIM2), and members of the Orai protein family (Orai1, 2, and 3) in prostate cancer. Moreover, we introduce new research models that promise to provide insights into whether dysregulated SOCE signaling has clinically relevant implications in terms of increasing the migration and invasion of prostate cancer cells. RECENT FINDINGS: Recent reports on Orai1 and Orai3 expression levels and function were in part controversial probably due to the heterogeneous nature of prostate cancer. Lately, in prostate cancer cells, transient receptor melastatin 4 channel was shown to alter SOCE and play a role in migration and proliferation. We specifically highlight new cancer research models: a subpopulation of cells that show tumor initiation and metastatic potential in mice and zebrafish models. SUMMARY: This review focuses on SOCE component dysregulation in prostate cancer and analyzes several preclinical, cellular, and animal cancer research models.
ABSTRACT
After myocardial infarction in humans, lost cardiomyocytes are replaced by an irreversible fibrotic scar. In contrast, zebrafish hearts efficiently regenerate after injury. Complete regeneration of the zebrafish heart is driven by the strong proliferation response of its cardiomyocytes to injury. Here we show that, after cardiac injury in zebrafish, telomerase becomes hyperactivated, and telomeres elongate transiently, preceding a peak of cardiomyocyte proliferation and full organ recovery. Using a telomerase-mutant zebrafish model, we found that telomerase loss drastically decreases cardiomyocyte proliferation and fibrotic tissue regression after cryoinjury and that cardiac function does not recover. The impaired cardiomyocyte proliferation response is accompanied by the absence of cardiomyocytes with long telomeres and an increased proportion of cardiomyocytes showing DNA damage and senescence characteristics. These findings demonstrate the importance of telomerase function in heart regeneration and highlight the potential of telomerase therapy as a means of stimulating cell proliferation upon myocardial infarction.
Subject(s)
Heart/physiology , Regeneration , Telomerase/physiology , Zebrafish Proteins/physiology , Animals , Cell Proliferation , Gene Expression , Gene Knockout Techniques , Myocardium/enzymology , Myocytes, Cardiac/physiology , Tissue Culture Techniques , ZebrafishABSTRACT
AIMS: While zebrafish embryos are amenable to in vivo imaging, allowing the study of morphogenetic processes during development, intravital imaging of adults is hampered by their small size and loss of transparency. The use of adult zebrafish as a vertebrate model of cardiac disease and regeneration is increasing at high speed. It is therefore of great importance to establish appropriate and robust methods to measure cardiac function parameters. METHODS AND RESULTS: Here we describe the use of 2D-echocardiography to study the fractional volume shortening and segmental wall motion of the ventricle. Our data show that 2D-echocardiography can be used to evaluate cardiac injury and also to study recovery of cardiac function. Interestingly, our results show that while global systolic function recovered following cardiac cryoinjury, ventricular wall motion was only partially restored. CONCLUSION: Cryoinjury leads to long-lasting impairment of cardiac contraction, partially mimicking the consequences of myocardial infarction in humans. Functional assessment of heart regeneration by echocardiography allows a deeper understanding of the mechanisms of cardiac regeneration and has the advantage of being easily transferable to other cardiovascular zebrafish disease models.
Subject(s)
Cold Temperature/adverse effects , Echocardiography/methods , Heart Ventricles/physiopathology , Myocardial Infarction/prevention & control , Regeneration/physiology , Ventricular Dysfunction/diagnosis , Ventricular Dysfunction/prevention & control , Animals , Myocardial Infarction/etiology , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Ventricular Dysfunction/etiology , Zebrafish/growth & developmentABSTRACT
The epicardium is the mesothelial outer layer of the vertebrate heart. It plays an important role during cardiac development by, among other functions, nourishing the underlying myocardium, contributing to cardiac fibroblasts and giving rise to the coronary vasculature. The epicardium also exerts key functions during injury responses in the adult and contributes to cardiac repair. In this article, we review current knowledge on the cellular and molecular mechanisms underlying epicardium formation in the zebrafish, a teleost fish, which is rapidly gaining status as an animal model in cardiovascular research, and compare it with the mechanisms described in other vertebrate models. We moreover describe the expression patterns of a subset of available zebrafish Wilms' tumor 1 transgenic reporter lines and discuss their specificity, applicability and limitations in the study of epicardium formation.
