1,721,162 research outputs found
A Purinergic Trail for Metastases
Full text linkNucleotides and nucleosides have emerged as important modulators of tumor biology. Recently acquired evidence shows that, when these molecules are released by cancer cells or surrounding tissues, they act as potent prometastatic factors, favoring tumor cell migration and tissue colonization. Therefore, nucleotides and nucleosides should be considered as a new class of prometastatic factors. In this review, we focus on the prometastatic roles of nucleotides and discuss future applications of purinergic signaling modulation in view of antimetastatic therapies
Myeloid cells in the tumor microenvironment: Role of adenosine
Full text linkAdenosine, deriving from ATP released by dying cancer cells and then degradated in the tumor environment by CD39/CD73 enzyme axis, is linked to the generation of an immunosuppressed niche favoring the onset of neoplasia. The effects of adenosine are mediated by four adenosine receptors, named A1, A2A, A2B and A3 that are widely expressed on several immune cell populations. A critical role of this nucleoside is emerging in the modulation of myeloid cell subsets accumulation and functions into tumor microenvironment, providing new insights that might be useful for the development of novel therapeutic approaches aimed to undermine the immune privileged sites where cancer cells grow and proliferate
Adenosine pathway and cancer: where do we go from here?
No full textIncreasing evidence supports the occurrence of an intriguing link between tumor
onset and development with the microenvironment in which cancer cells are embedded. In this context, a critical role of CD73, in calibrating the duration, magnitude and composition of adenosine signaling in cancer development and progression, has been identified. Adenosine levels are increased in cancer tissues as the result of genetic alterations that occur during tumor progression.
Indeed, a rearrangement of the adenosine metabolic machinery has been described within the neoplastic milieu with the aim of amplifying adenosine generation, thereby creating an immune tolerant microenvironment suitable for tumor onset and development. At the same time, adenosine, through the engagement of receptors expressed on neoplastic cells, finely tunes the growth and dissemination of tumor
mass, thus interfering with cancer proliferation, apoptosis and metastasis. Based on current knowledge, an improved understanding of how and to what extent adenosine participates to the molecular mechanisms underlying cancer development and diffusion will pave the way toward new therapeutic advances. The discovery and development of drugs targeted on this system might lead to substantial improvements in the clinical management of various cancers
Pharmacological modulation of adenosine receptor pathways and inflammatory disorders: the way towards novel therapeutics?
No full textAbstract non previsto dalla rivista per questo tipo di articol
Anti-CD73 in cancer immunotherapy: awakening new opportunities
No full textIn recent years, cancer immunotherapy made significant advances due to a better understanding of the principles underlying tumor biology and immunology. In this context, CD73 is a key molecule, since via degradation of adenosine monophosphate into adenosine, endorses the generation of an immunosuppressed and pro-angiogenic niche within the tumor microenvironment that promotes the onset and progression of cancer. Targeting CD73 results in favorable antitumor effects in pre-clinical models and combined treatments of CD73 blockade with other immune-modulating agents (i.e. anti-CTLA-4 mAb or anti-PD1 mAb) is particularly attractive. Although there is still a long way to go, anti-CD73 therapy, through the development of CD73 monoclonal antibodies, can potentially constitute a new biologic therapy for cancer patients. In this review, we discuss the link between CD73 and the onset, development and spread of tumors, highlighting the potential value of this molecule as a target and as a novel biomarker in the context of personalized cancer therapy
A holistic view of adenosine pathways in the control of intestinal neuromuscular functions: the enteric purinome concept
No full textAdenosine is involved in the modulation of enteric neuromuscular functions, operating a fine tuning of smooth muscle contractility, peristaltic reflex and transit. In this issue of the BJP, Zizzo et al. report novel findings on the expression of adenosine receptors in mouse duodenum, extending our knowledge of their involvement in the control of spontaneous and neurogenic intestinal motility. In this study, particular attention was paid to the differential activation of adenosine receptors, as a result of their interplay with regulatory systems, modulating the availability of endogenous adenosine in a compartmentalised manner. This evidence will contribute to the holistic evaluation of the role played by adenosine in the regulation of intestinal motility, in accordance with the novel concept of the enteric 'purinome'. This commentary discusses the role of the 'purinome' in the modulation of enteric neuromuscular activity, pointing out its involvement in the intestinal neuroplasticity associated with bowel dysmotility
Rethinking Communication in the Immune System: The Quorum Sensing Concept
No full textQuorum sensing was first described as the communication process bacteria employ to coordinate changes in gene expression and therefore, their collective behavior in response to population density. Emerging new evidence suggests that quorum sensing can also contribute to the regulation of immune cell responses. Quorum sensing might be achieved by the ability of immune cells to perceive the density of their own populations or those of other cells in their environment; responses to alterations in cell density might then be coordinated via changes in gene expression and protein signaling. Quorum sensing mechanisms can regulate T and B cell as well as macrophage function. We posit that perturbations in quorum sensing may undermine the balance between diverse immune cell populations and predispose the host to immune abnormalities
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