1,721,030 research outputs found
Giulio Gabbiani and the discovery of myofibroblasts
No full textMyofibroblasts, specialized fibroblasts expressing the protein alpha-smooth muscle actin, are instrumental in wound contraction during normal wound healing. Tissue shortening is then stabilized by the synthesis of extracellular matrix, collagen in particular. Alpha-smooth muscle actin within myofibroblasts becomes organized in filamentous bundles, called stress fibers, that allow the retractile movement producing wound contraction. During hypertrophic scarring, skin deformations depend on the inappropriate action of these stress fibers that for unknown reasons persist even after the epithelialization of the wound. This historical review article is dedicated to the reconstruction of the discovery of this cell by the Italian scientist Giulio Gabbiani
Update in TIGIT Immune-Checkpoint Role in Cancer
Full text linkThe in-depth characterization of cross-talk between tumor cells and T cells in solid and hematological malignancies will have to be considered to develop new therapeutical strategies concerning the reactivation and maintenance of patient-specific antitumor responses within the patient tumor microenvironment. Activation of immune cells depends on a delicate balance between activating and inhibitory signals mediated by different receptors. T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor expressed by regulatory T cells (Tregs), activated T cells, and natural killer (NK) cells. TIGIT pathway regulates T cell-mediated tumor recognition in vivo and in vitro and represents an exciting target for checkpoint blockade immunotherapy. TIGIT blockade as monotherapy or in combination with other inhibitor receptors or drugs is emerging in clinical trials in patients with cancer. The purpose of this review is to update the role of TIGIT in cancer progression, looking at TIGIT pathways that are often upregulated in immune cells and at possible therapeutic strategies to avoid tumor aggressiveness, drug resistance, and treatment side effects. However, in the first part, we overviewed the role of immune checkpoints in immunoediting, the TIGIT structure and ligands, and summarized the key immune cells that express TIGIT
Cross talk between natural killer cells and mast cells in tumor angiogenesis
No full textNatural killer (NK) cells are large granular lymphocytes of the innate immune system, responsible for direct targeting and killing of both virally infected and transformed cells. Under pathological conditions and during inflammation, NK cells extravasate into the lymph nodes and accumulate at inflammatory or tumor sites. The activation of NK cells depends on an intricate balance between activating and inhibitory signals that determines if a target will be susceptible to NK-mediated lysis. Many experimental evidences indicate that NK cells are also involved in several immunoregulatory processes and have the ability to modulate the adaptive immune responses. Many other important aspects about NK cell biology are emerging in these last years. The aim of this review is to elucidate the role of NK cells in tumor angiogenesis and their interaction with mast cells. In fact, it has been observed that NK cells produce pro-angiogenic factors and participate alone or in cooperation with mast cells to the regulation of angiogenesis in both physiological and pathological conditions including tumors
The dual role of mast cells in tumor fate
No full textThe exact role of mast cells in tumor growth is not clear and multifaceted. In some cases, mast cells stimulate while in others inhibit this process. This dual role may be explained to some extent by the huge number of bioactive molecules stored in mast cell granules, as well as differences between tumor microenvironment, tumor type, and tumor phase of development
Epithelial-Mesenchymal Transition in Cancer: A Historical Overview
Full text linkEpithelial-mesenchymal transitions (EMTs), the acquisition of mesenchymal features from epithelial cells, occur during some biological processes and are classified into three types: the first type occurs during embryonic development, the second type is associated with adult tissue regeneration, and the third type occurs in cancer progression. EMT occurring during embryonic development in gastrulation, renal development, and the origin and fate of the neural crest is a highly regulated process, while EMT occurring during tumor progression is highly deregulated. EMT allows the solid tumors to become more malignant, increasing their invasiveness and metastatic activity. Secondary tumors frequently maintain the typical histologic characteristics of the primary tumor. These histologic features connecting the secondary metastatic tumors to the primary is due to a process called mesenchymal-epithelial transition (MET). MET has been demonstrated in different mesenchymal tumors and is the expression of the reversibility of EMT. EMT modulation could constitute an approach to avoid metastasis. Some of the targeted small molecules utilized as antiproliferative agents have revealed to inhibit EMT initiation or maintenance because EMT is regulated through signaling pathways for which these molecules have been designed
Hematopoietic growth factors and tumor angiogenesis
No full textAngiogenesis is regulated by numerous "classic" factors such as vascular endothelial growth factor (VEGF) and many other endogenous "non-classic"peptides, including erythropoietin (Epo), and granulocyte-/granulocyte macrophage colony stimulating factor (G-/GM-CSF). The latter play an important regulatory role in angiogenesis, especially under pathological conditions and constitute a crosslink between angiogenesis and hematopoiesis. This article reviews studies on the ability of hematopoietic cytokines to affect several endothelial cell functions in tumor angiogenesis. These findings in all these studies support the hypothesis formulated at the beginning of this century that a common ancestral cell, the hemangioblast, gives rise to cells of both the endothelial and the hematopoietic lineages
A revisited concept. Tumors: Wounds that do not heal
No full textIn 1986, Harold F. Dvorak, Professor of Pathology at Harvard Medical School Boston, published an essay in the New England Journal of Medicine entitled "Tumors: Wounds that do not heal" pointed out that similarities exist between tumor stroma generation and wound healing. Cancers share many features in common with tissue regeneration, including immune response, cell proliferation, cell migration, tissue remodeling, and cell death. In this review article, we analyze the importance and the limits of this concept, which confirm the close relationship between two apparently different biological processes
Bone niches, hematopoietic stem cells, and vessel formation
Full text linkBone marrow (BM) is a source of hematopoietic stem cells (HSCs). HSCs are localized in both the endosteum, in the so-called endosteal niche, and close to thin-walled and fenestrated sinusoidal vessel in the center of BM, in the so-called vascular niche. HSCs give rise to all types of mature blood cells through a process finely controlled by numerous signals emerging from the bone marrow niches where HSCs reside. This review will focus on the description of the role of BM niches in the control of the fate of HSCs and will also highlight the role of the BM niches in the regulation of vasculogenesis and angiogenesis. Moreover, alterations of the signals in niche microenvironment are involved in many aspects of tumor progression and vascularization and further knowledge could provide the basis for the development of new therapeutic strategies
The chick embryo chorioallantoic membrane as an in vivo experimental model to study human neuroblastoma
No full textThe chick embryo chorioallantoic membrane (CAM) has long been a favored system for the study of tumor angiogenesis because at the stage of development when generally tumor grafts are placed (6-10 days of incubation), the chick's immunocompetent system is not fully developed and the conditions for rejection have not yet been established. All studies for mammalian neoplasms, including neuroblastoma, have used tumor cell lines, tumor bioptic specimens, cell suspensions derived from tumors, and mouse tumor xenografts bioptic specimens. CAM can also be used to study the effects of antiangiogenic molecules on tumor cell suspensions of tumor bioptic specimens. This review article summarizes and discusses the literature data on the use of the CAM as an in vivo experimental model to study human neuroblastoma
Vascular co-option in resistance to anti-angiogenic therapy
No full textThree different mechanisms of neovascularization have been described in tumor growth, including sprouting angiogenesis, intussusceptive microvascular growth and glomeruloid vascular proliferation. Tumors can also grow by means of alternative mechanisms including vascular co-option, vasculogenic mimicry, angiotropism, and recruitment of endothelial precursor cells. Vascular co-option occurs in tumors independently of sprouting angiogenesis and the non-angiogenic cancer cells are described as exploiting pre-existing vessels. Vascular co-option is more frequently observed in tumors of densely vascularized organs, including the brain, lung and liver, and vascular co-option represents one of the main mechanisms involved in metastasis, as occurs in liver and lung, and resistance to anti-angiogenic therapy. The aim of this review article is to analyze the role of vascular co-option as mechanism through which tumors develop resistance to anti-angiogenic conventional therapeutic approaches and how blocking co-option can suppress tumor growth
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