Alterations in Calcium Signaling Pathways in Breast Cancer

Breast cancer is the second most common cancer in women and the fifth cause contributing to death due to the cancer condition. It is essential to deeply understand the complex cellular mechanisms leading to this disease. There are multiple connections between calcium homeostasis alterations and breast cancer in the literature, but no consensus links the mechanism to the disease prognosis. Among the cells contributing to the breast cancer are the breast telocytes, which connect through gap junctions to other cells, including cancer cells and myoepithelial cells. Multiple proteins (i.e., voltage-gated calcium channels, transient receptor potential channels, STIM and Orai proteins, ether à go-go potassium channels, calcium-activated potassium channels, calcium-activated chloride channels, muscarinic acetylcholine receptors, etc.) coupled with calcium signaling pathways undergo functional and/or expression changes associated with breast cancer development and progression, and might represent promising pharmacological targets. Unraveling the mechanisms of altered calcium homeostasis in various breast cells due to the cancer condition might contribute to personalized therapeutic approaches

Extracellular Vesicles in Cancer

Extracellular vesicles (EVs) represent a generic term for all the secreted vesicles, which include exosomes, microvesicles, and apoptotic bodies. EVs are key partners in the intercellular communication and play an essential role in multiple physiological and pathological conditions. EVs are shuttles for cargo molecules, such as RNA (mRNA, microRNA, and other noncoding RNAs), DNA, proteins (receptors, transcription factors, enzymes, and extracellular matrix proteins), and lipids. In pathological states, including cancer, EVs might represent either useful biomarkers or can be used for therapeutic purposes. Moreover, in cancer, it was demonstrated that EVs play an essential role in drug resistance. Here, we review the role played by EVs in the most common forms of cancer, with a special focus on ovarian and breast cancers

Telocytes: New Connecting Devices in the Stromal Space of Organs

Telocytes (TCs) represent a new type of interstitial cells, and were discovered by Prof. Popescu and his collaborators from Bucharest in 2005, and described as Interstitial Cajal-Like Cells (ICLCs). In 2010, Prof. Popescu and Prof. Faussone-Pellegrini from Florence, based on their expertise in morphology, agreed that in fact ICLCs were a brand-new entity and they renamed them telocytes. TCs are characterized by specific veil- or ribbon-like extensions called telopodes. Telopodes aid TCs in forming homo- or hetero-cellular contacts; thus, assembling three-dimensional networks that organizes the stromal and the parenchymal components of the organs. TCs can transfer information to neighbor cells ensuring a short-distance communication, and remotely by the release a wide variety of extracellular vesicles: exosomes, ectosomes, and multivesicular bodies. Here, we reviewed the evolution of the interest regarding TCs in different organs, in normal and pathological conditions. The main focus was on the role of TCs in gastrointestinal tract, urinary bladder, reproductive tract, and heart. This chapter sums up information about the possibilities that TCs are capable to behave as sensors/mediators in nervous activity, to represent mesenchymal stem cell precursors in adulthood, and to control and determine the differentiation/maturation of other cell types either during development or in postnatal life

Calcium signaling in interstitial cells: focus on telocytes

In this review, we describe the current knowledge on calcium signaling pathways in interstitial cells with a special focus on interstitial cells of Cajal (ICCs), interstitial Cajal-like cells (ICLCs), and telocytes. In detail, we present the generation of Ca(2+) oscillations, the inositol triphosphate (IP\u2083)/Ca(2+) signaling pathway and modulation exerted by cytokines and vasoactive agents on calcium signaling in interstitial cells. We discuss the physiology and alterations of calcium signaling in interstitial cells, and in particular in telocytes. We describe the physiological contribution of calcium signaling in interstitial cells to the pacemaking activity (e.g., intestinal, urinary, uterine or vascular pacemaking activity) and to the reproductive function. We also present the pathological contribution of calcium signaling in interstitial cells to the aortic valve calcification or intestinal inflammation. Moreover, we summarize the current knowledge of the role played by calcium signaling in telocytes in the uterine, cardiac and urinary physiology, and also in various pathologies, including immune response, uterine and cardiac pathologies

Skeletal Muscle Stem Cell Niche from Birth to Old Age

Stem cells are defined as undifferentiated cells that are able to unlimitedly renew themselves within controlled conditions and to differentiate into a multitude of mature cell types. Skeletal muscle stem cells, represented predominantly by satellite cells, show a variable capability of self-renewal and myogenic differentiation. They were found to be involved not only in the growth of myofibers during neonatal and juvenile life but also in the regeneration of skeletal muscles after an injury. The microenvironment in which stem cells are nourished and maintained dormant preceding division and differentiation is known as “niche.” The niche consists of myofibers, which are believed to modulate the active/inactive state of the stem cells, extracellular matrix, neural networks, blood vessels, and a multitude of soluble molecules. It was observed that changes in the composition of the niche have an impact on the stem cell functions and hierarchy. Furthermore, it seems that its layout is variable throughout the entire life, translating into a decrease in the regenerative capacity of satellite cells in aged tissues. The scope of this chapter is to provide a detailed view of the changes that occur in the skeletal stem cell niche during life and to analyze their implications on tissue regeneration. Future studies should focus on developing new therapeutic tools for diseases involving muscle atrophy

Intestinal Microbiomics in Physiological and Pathological Conditions

Microbiomics represents a new science studying the microbiome, consisting of all the microorganisms of a given community. This new science collects data about all the members of the microbial community and quantifies the molecules responsible for the structure, function, and dynamics of the microbiome. The human microbiome plays a very important role in the healthy state and in a variety of disease states. The human microbiome knowledge has evolved during the last decades and nowadays one can consider that, in particular, the gut microbiota is seen as a significant organ holding 150 times more genes compared to the human genome. This chapter will focus on discussing the normal and modified phyla and species of the gut microbiome in a variety of conditions, providing a better understanding of host-microbiome interactions. We will highlight some new associations between intestinal dysbiosis and acute or chronic inflammatory and metabolic diseases

Telocytes and Other Interstitial Cells 2.0: From Structure to Function

Interstitial cells are often seen as those cells that fill the space between parenchymal cells, responsible for fulfilling the function of an organ [...

Uterine Telocytes: A Review of Current Knowledge1

Telocytes (TCs), a novel cell type, are briefly defined as interstitial cells with telopodes (Tps). However, a specific immunocytochemical marker has not yet been found; therefore, electron microscopy is currently the only accurate method for identifying TCs. TCs are considered to have a mesenchymal origin. Recently proteomic analysis, microarray-based gene expression analysis, and the micro-RNA signature clearly showed that TCs are different from fibroblasts, mesenchymal stem cells, and endothelial cells. The dynamics of Tps were also revealed, and some electrophysiological properties of TCs were described (such as membrane capacitance, input resistance, membrane resting potential, and absence of action potentials correlated with different ionic currents characteristics), which can be used to distinguish uterine TCs from smooth muscle cells (SMCs). Here, we briefly present the most recent findings on the characteristics of TCs and their functions in human pregnant and nonpregnant uteri

Uterine telocytes: a review of current knowledge

Telocytes (TCs), a novel cell type, are briefly defined as interstitial cells with telopodes (Tps). However, a specific immunocytochemical marker has not yet been found; therefore, electron microscopy is currently the only accurate method for identifying TCs. TCs are considered to have a mesenchymal origin. Recently proteomic analysis, microarray-based gene expression analysis, and the micro-RNA signature clearly showed that TCs are different from fibroblasts, mesenchymal stem cells, and endothelial cells. The dynamics of Tps were also revealed, and some electrophysiological properties of TCs were described (such as membrane capacitance, input resistance, membrane resting potential, and absence of action potentials correlated with different ionic currents characteristics), which can be used to distinguish uterine TCs from smooth muscle cells (SMCs). Here, we briefly present the most recent findings on the characteristics of TCs and their functions in human pregnant and nonpregnant uteri