1,721,053 research outputs found
Prostate Cancer and Bone: The Elective Affinities
Full text linkThe onset of metastases dramatically changes the prognosis of prostate cancer patients, determining increased morbidity and a drastic fall in survival expectancy. Bone is a common site of metastases in few types of cancer, and it represents the most frequent metastatic site in prostate cancer. Of note, the prevalence of tumor relapse to the bone appears to be increasing over the years, likely due to a longer overall survival of prostate cancer patients. Bone tropism represents an intriguing challenge for researchers also because the preference of prostate cancer cells for the bone is the result of a sequential series of targetable molecular events. Many factors have been associated with the peculiar ability of prostate cancer cells to migrate in bone marrow and to determine mixed osteoblastic/osteolytic lesions. As anticipated by the success of current targeted therapy aimed to block bone resorption, a better understanding of molecular affinity between prostate cancer and bone microenvironment will permit us to cure bone metastasis and to improve prognosis of prostate cancer patients
How the "seed" prepares the "soil": The bone/bone marrow pre-metastatic niche
Full text linkCancer is one of the leading causes of death in women and men worldwide. The fatal outcome usually occurs after metastatic dissemination, and bone is by far the most common site of metastasis for breast and prostate cancer, the highest incidence neoplasia in women and men, respectively. However, while this is clear, the mechanisms through which the metastatic preference is established is not. An emerging concept in this regard is the premetastatic niche (PMN) establishment, i.e., the process through which tumors can influence the bone microenvironment from the primary site and make it permissive for their engraftment, before they migrate to the blood flow and metastasize. In this review, we discuss key microenvironmental players in the bone/bone marrow PMN, including osteoblasts, osteoclasts, and bone marrow adipocytes. We also describe the known PMNeducating factors, as well as the role of extracellular vesicles as emerging players in the bone/bone marrow PMN. An overview of current therapeutic developments aimed at targeting the bone PMN is also provided
Editorial: Extracellular vesicles as modulators of cancer cell adaptive responses linked to therapy resistance
Full text linkNo abstract availabl
Tumour-Derived Extracellular Vesicles (EVs): A Dangerous “Message in A Bottle” for Bone
No full textSeveral studies have shown the importance of Extracellular Vesicles (EVs) in the intercellular communication between tumour and resident cells. Through EVs, tumour cells can trigger cell-signalling molecules and shuttle exogenous information to target cells, thus promoting spread of the disease. In fact, many processes are fuelled by EVs, such as tumour invasion and dormancy, drug-resistance, immune-surveillance escape, extravasation, extracellular matrix remodelling and metastasis. A key element is certainly the molecular profile of the shed cargo. Understanding the biochemical basis of EVs would help to predict the ability and propensity of cancer cells to metastasize a specific tissue, with the aim to target the release of EVs and to manipulate their content as a possible therapeutic approach. Moreover, EV profiling could help monitor the progression of cancer, providing a useful tool for more effective therapy. This review will focus on all the EV-mediated mentioned mechanisms in the context of both primary bone cancers and bone metastases
Switching Homes: How Cancer Moves to Bone
Full text linkBone metastases (BM) are a very common complication of the most prevalent human cancers. BM are extremely painful and may be life-threatening when associated with hypercalcaemia. BM can lead to kidney failure and cardiac arrhythmias and arrest, but why and how do cancer cells decide to “switch homes” and move to bone? In this review, we will present what answers science has provided so far, with focus on the molecular mechanisms and cellular aspects of well-established findings, such as the concept of “vicious cycle” and “osteolytic” vs. “osteosclerotic” bone metastases; as well as on novel concepts, such as cellular dormancy and extracellular vesicles. At the molecular level, we will focus on hypoxia-associated factors and angiogenesis, the Wnt pathway, parathyroid hormone-related peptide (PTHrP) and chemokines. At the supramolecular/cellular level, we will discuss tumour dormancy, id est the mechanisms through which a small contingent of tumour cells coming from the primary site may be kept dormant in the endosteal niche for many years. Finally, we will present a potential role for the multimolecular mediators known as extracellular vesicles in determining bone-tropism and establishing a premetastatic niche by influencing the bone microenvironment
Bone cells and the mechanisms of bone remodelling
No full text""Bone is a peculiar connective tissue which. functionally interacts with many other organs and tissues,. including bone marrow, lymphoid tissue, kidney, adipose. tissue, endocrine pancreas, brain and gonads. Bone functions. are accomplished by three principal cell types: the osteoblasts,. cells of mesenchymal origin having osteogenic functions, the. osteoclasts, giant multinucleated cells arising from the. monocyte-macrophage line and devoted to resorb bone, and. the osteocytes, the latter arising from mature osteoblasts that,. once deposited the bone matrix, remain trapped in it, becoming. quiescent cells. Osteocytes are known for their role as. mechanosensors, however, old and new evidence showed their. active contribution to mineral homeostasis. Moreover, the. cross-talk between bone cells is crucial, since a correct bone. homeostasis relies on a right coupling between osteoblast and. osteoclast functions. Any deregulation of this coupling is. responsible for bone disease condition, which reflects on other. organs with which bone interacts."
Osteoblast Differentiation and Signaling: Established Concepts and Emerging Topics
Full text linkOsteoblasts, the cells that build up our skeleton, are remarkably versatile and important cells that need tight regulation in all the phases of their differentiation to guarantee proper skeletal development and homeostasis. Although we know many of the key pathways involved in osteoblast differentiation and signaling, it is becoming clearer and clearer that this is just the tip of the iceberg, and we are constantly discovering novel concepts in osteoblast physiology. In this review, we discuss well-established pathways of osteoblastic differentiation, i.e., the classical ones committing mesenchymal stromal cells to osteoblast, and then osteocytes as well as recently emerged players. In particular, we discuss micro (mi)RNAs, long non-coding (lnc)RNAs, circular (circ)RNAs, and extracellular vesicles, focusing on the mechanisms through which osteoblasts are regulated by these factors, and conversely, how they use extracellular vesicles to communicate with the surrounding microenvironment
Updates on Osteoimmunology: What's New on the Cross-Talk Between Bone and Immune System
Full text linkThe term osteoimmunology was coined many years ago to describe the research field that deals with the cross-regulation between bone cells and the immune system. As a matter of fact, many factors that are classically considered immune-related, such as InterLeukins (i.e., IL-6, -11, -17, and -23), Tumor Necrosis Factor (TNF)-α, Receptor-Activator of Nuclear factor Kappa B (RANK), and its Ligand (RANKL), Nuclear Factor of Activated T-cell, cytoplasmatic-1 (NFATc1), and others have all been found to be crucial in osteoclast and osteoblast biology. Conversely, bone cells, which we used to think would only regulate each other and take care of remodeling bone, actually regulate immune cells, by creating the so-called “endosteal niche.” Both osteoblasts and osteoclasts participate to this niche, either by favoring engraftment, or mobilization of Hematopoietic Stem Cells (HSCs). In this review, we will describe the main milestones at the base of the osteoimmunology and present the key cellular players of the bone-immune system cross-talk, including HSCs, osteoblasts, osteoclasts, bone marrow macrophages, osteomacs, T- and B-lymphocytes, dendritic cells, and neutrophils. We will also briefly describe some pathological conditions in which the bone-immune system cross-talk plays a crucial role, with the final aim to portray the state of the art in the mechanisms regulating the bone-immune system interplay, and some of the latest molecular players in the field. This is important to encourage investigation in this field, to identify new targets in the treatment of bone and immune diseases
Extracellular Vesicles in Bone Tumors: How to Seed in the Surroundings Molecular Information for Malignant Transformation and Progression
Full text linkBone is a very dynamic tissue hosting different cell types whose functions are regulated by a plethora of membrane-bound and soluble molecules. Intercellular communication was recently demonstrated to be also sustained by the exchange of extracellular vesicles (EVs). These are cell-derived nanosized structures shuttling biologically active molecules, such as nucleic acids and proteins. The bone microenvironment is a preferential site of primary and metastatic tumors, in which cancer cells find a fertile soil to “seed and blossom”. Nowadays, many oncogenic processes are recognized to be sustained by EVs. For example, EVs can directly fuel the vicious cycle in the bone/bone marrow microenvironment. EVs create a favourable environment for tumor growth by affecting osteoblasts, osteoclasts, osteocytes, adipocytes, leukocytes, and endothelial cells. At the same time other crucial tumor-mediated events, such as the premetastatic niche formation, tumor cell dormancy, as well as drug resistance, have been described to be fostered by tumor-derived EVs. In this review, we will discuss the main body of literature describing how the cancer cells use the EVs for their growth into the bone and for educating the bone microenvironment to host metastases
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