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  1. Article ; Online: Experimental Approaches for Studying Semaphorin Signals in Tumor Growth and Metastasis in Mouse Models.

    Moiso, Enrico / Accardo, Massimo / Tamagnone, Luca

    Methods in molecular biology (Clifton, N.J.)

    2017  Volume 1493, Page(s) 467–484

    Abstract: Tumor growth and metastatic dissemination are complex multistep processes. They clearly depend on the intrinsic behavior of cancer cells, but are remarkably influenced by a variety of stromal cells present in the tumor microenvironment, which include ... ...

    Abstract Tumor growth and metastatic dissemination are complex multistep processes. They clearly depend on the intrinsic behavior of cancer cells, but are remarkably influenced by a variety of stromal cells present in the tumor microenvironment, which include those implicated in tumor angiogenesis, as well as bone marrow-derived cells recruited from the circulation. Moreover, multiple molecular signals exchanged between cancer cells and non-neoplastic stromal cells control tumor growth and metastasis; notably, members of the semaphorin family are emerging players in this scenario.In vivo tumor models represent the best setting for studying metastatic tumor progression, as they allow recapitulating the contribution of multiple cell types and signaling molecules in a complex tissue context, subject to pathophysiological local and systemic responses, such as metabolic changes, hypoxia, necrosis, fibrosis, inflammation, and cytokine release. Here, we describe some experimental approaches based on murine models to study the role of semaphorin signaling in tumor growth and metastatic progression in vivo.
    Language English
    Publishing date 2017
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-6448-2_33
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Dynamic Interplay between Pericytes and Endothelial Cells during Sprouting Angiogenesis.

    Chiaverina, Giulia / di Blasio, Laura / Monica, Valentina / Accardo, Massimo / Palmiero, Miriam / Peracino, Barbara / Vara-Messler, Marianela / Puliafito, Alberto / Primo, Luca

    Cells

    2019  Volume 8, Issue 9

    Abstract: Vascular physiology relies on the concerted dynamics of several cell types, including pericytes, endothelial, and vascular smooth muscle cells. The interactions between such cell types are inherently dynamic and are not easily described with static, ... ...

    Abstract Vascular physiology relies on the concerted dynamics of several cell types, including pericytes, endothelial, and vascular smooth muscle cells. The interactions between such cell types are inherently dynamic and are not easily described with static, fixed, experimental approaches. Pericytes are mural cells that support vascular development, remodeling, and homeostasis, and are involved in a number of pathological situations including cancer. The dynamic interplay between pericytes and endothelial cells is at the basis of vascular physiology and few experimental tools exist to properly describe and study it. Here we employ a previously developed ex vivo murine aortic explant to study the formation of new blood capillary-like structures close to physiological situation. We develop several mouse models to culture, identify, characterize, and follow simultaneously single endothelial cells and pericytes during angiogenesis. We employ microscopy and image analysis to dissect the interactions between cell types and the process of cellular recruitment on the newly forming vessel. We find that pericytes are recruited on the developing sprout by proliferation, migrate independently from endothelial cells, and can proliferate on the growing capillary. Our results help elucidating several relevant mechanisms of interactions between endothelial cells and pericytes.
    MeSH term(s) Animals ; Aorta/cytology ; Aorta/metabolism ; Endothelial Cells/cytology ; Endothelial Cells/metabolism ; Mice ; Mice, Transgenic ; Neovascularization, Physiologic ; Pericytes/cytology ; Pericytes/metabolism
    Language English
    Publishing date 2019-09-19
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells8091109
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Reverse signaling by semaphorin 4C elicits SMAD1/5- and ID1/3-dependent invasive reprogramming in cancer cells.

    Gurrapu, Sreeharsha / Franzolin, Giulia / Fard, Damon / Accardo, Massimo / Medico, Enzo / Sarotto, Ivana / Sapino, Anna / Isella, Claudio / Tamagnone, Luca

    Science signaling

    2019  Volume 12, Issue 595

    Abstract: Semaphorins are a family of molecular signals that guide cell migration and are implicated in the regulation of cancer cells. In particular, transmembrane semaphorins are postulated to act as both ligands ("forward" mode) and signaling receptors (" ... ...

    Abstract Semaphorins are a family of molecular signals that guide cell migration and are implicated in the regulation of cancer cells. In particular, transmembrane semaphorins are postulated to act as both ligands ("forward" mode) and signaling receptors ("reverse" mode); however, reverse semaphorin signaling in cancer is relatively less understood. Here, we identified a previously unknown function of transmembrane semaphorin 4C (Sema4C), acting in reverse mode, to elicit nonconventional TGF-β/BMP receptor activation and selective SMAD1/5 phosphorylation. Sema4C coimmunoprecipitated with TGFBRII and BMPR1, supporting its role as modifier of this pathway. Sema4C reverse signaling led to the increased abundance of ID1/3 transcriptional factors and to extensive reprogramming of gene expression, which suppressed the typical features of the epithelial-mesenchymal transition in invasive carcinoma cells. This phenotype was nevertheless coupled with burgeoning metastatic behavior in vivo, consistent with evidence that Sema4C expression correlates with metastatic progression in human breast cancers. Thus, Sema4C reverse signaling promoted SMAD1/5- and ID1/3-dependent gene expression reprogramming and phenotypic plasticity in invasive cancer cells.
    MeSH term(s) Animals ; COS Cells ; Chlorocebus aethiops ; Humans ; Inhibitor of Differentiation Protein 1/genetics ; Inhibitor of Differentiation Protein 1/metabolism ; Inhibitor of Differentiation Proteins/genetics ; Inhibitor of Differentiation Proteins/metabolism ; Neoplasm Invasiveness ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; PC-3 Cells ; Semaphorins/genetics ; Semaphorins/metabolism ; Signal Transduction ; Smad1 Protein/genetics ; Smad1 Protein/metabolism ; Smad3 Protein/genetics ; Smad3 Protein/metabolism
    Chemical Substances ID1 protein, human ; Inhibitor of Differentiation Protein 1 ; Inhibitor of Differentiation Proteins ; Neoplasm Proteins ; SMAD1 protein, human ; SMAD3 protein, human ; Sema4c protein, human ; Semaphorins ; Smad1 Protein ; Smad3 Protein ; ID3 protein, human (147785-34-0)
    Language English
    Publishing date 2019-08-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2417226-1
    ISSN 1937-9145 ; 1945-0877
    ISSN (online) 1937-9145
    ISSN 1945-0877
    DOI 10.1126/scisignal.aav2041
    Database MEDical Literature Analysis and Retrieval System OnLINE

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