For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
73
views
43
references
 Top references
cited by
16
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      496
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      Sphingosine-1-Phosphate Receptor 1 in Classical Hodgkin Lymphoma: Assessment of Expression and Role in Cell Migration

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Classical Hodgkin lymphoma (CHL), a neoplasm of abnormal B lymphocytes (Hodgkin-Reed Sternberg cells), has been described to have a typical pattern of clinical presentation and dissemination often involving functionally contiguous lymph nodes. Despite the progress made in understanding CHL pathophysiology, the factors which regulate the spread of lymphoma cells in CHL are poorly understood. Sphingosine-1-Phosphate (S1P), a bioactive sphingolipid present at high concentrations in plasma and lymphatic fluid, is known to play a critical role in regulating lymphocyte trafficking mainly through S1PR1. In this study, we explore the role of the S1P-S1PR1 axis in Hodgkin lymphoma cell migration and the expression of S1PR1 in CHL cell lines and clinical cases. We found that S1PR1 is present in the KM-H2 and SUP-HD1 Hodgkin lymphoma cell lines at the mRNA and protein level. In addition, functionally, S1P potently stimulated migration of both cell lines. S1P-induced migration was inhibited by the S1PR1 antagonist, VPC44116 and the S1PR1 functional antagonist, FTY720-P, but was potentiated by the S1PR2 specific antagonist, JTE013. We also determined that S1PR1 induced migration in the KM-H2 and SUP-HD1 cells via the heterotrimeric G protein G i and the phosphatidylinositol-3-kinase (PI3K) pathway. Immunohistochemical assessment of tissue from CHL samples revealed that a subset of cases (7/57; 12%) show strong, membranous staining for S1PR1 in Hodgkin-Reed Sternberg cells.

          Altogether our data indicate that S1PR1 is a functional receptor on Hodgkin-Reed Sternberg cells which governs tumor cell migration and is expressed in a subset of CHL cases. Given the availability of S1PR1 antagonists, some of which are used clinically for modulation of the immune system, these results suggest that S1PR1 could be a future therapeutic target in the treatment of those cases of S1PR1-positive, refractory/recurrent CHL.

          Related collections

          Most cited references43

          • Record: found
          • Abstract: found
          • Article: not found

          Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1.

          Mehrdad Matloubian, Charles G. Lo, Guy Cinamon … (2004)
          Adaptive immunity depends on T-cell exit from the thymus and T and B cells travelling between secondary lymphoid organs to survey for antigens. After activation in lymphoid organs, T cells must again return to circulation to reach sites of infection; however, the mechanisms regulating lymphoid organ exit are unknown. An immunosuppressant drug, FTY720, inhibits lymphocyte emigration from lymphoid organs, and phosphorylated FTY720 binds and activates four of the five known sphingosine-1-phosphate (S1P) receptors. However, the role of S1P receptors in normal immune cell trafficking is unclear. Here we show that in mice whose haematopoietic cells lack a single S1P receptor (S1P1; also known as Edg1) there are no T cells in the periphery because mature T cells are unable to exit the thymus. Although B cells are present in peripheral lymphoid organs, they are severely deficient in blood and lymph. Adoptive cell transfer experiments establish an intrinsic requirement for S1P1 in T and B cells for lymphoid organ egress. Furthermore, S1P1-dependent chemotactic responsiveness is strongly upregulated in T-cell development before exit from the thymus, whereas S1P1 is downregulated during peripheral lymphocyte activation, and this is associated with retention in lymphoid organs. We find that FTY720 treatment downregulates S1P1, creating a temporary pharmacological S1P1-null state in lymphocytes, providing an explanation for the mechanism of FTY720-induced lymphocyte sequestration. These findings establish that S1P1 is essential for lymphocyte recirculation and that it regulates egress from both thymus and peripheral lymphoid organs.
          Article 0 comments Cited 671 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists.

            Suzanne Mandala, Richard Hajdu, James Bergstrom … (2002)
            Blood lymphocyte numbers, essential for the development of efficient immune responses, are maintained by recirculation through secondary lymphoid organs. We show that lymphocyte trafficking is altered by the lysophospholipid sphingosine-1-phosphate (S1P) and by a phosphoryl metabolite of the immunosuppressive agent FTY720. Both species were high-affinity agonists of at least four of the five S1P receptors. These agonists produce lymphopenia in blood and thoracic duct lymph by sequestration of lymphocytes in lymph nodes, but not spleen. S1P receptor agonists induced emptying of lymphoid sinuses by retention of lymphocytes on the abluminal side of sinus-lining endothelium and inhibition of egress into lymph. Inhibition of lymphocyte recirculation by activation of S1P receptors may result in therapeutically useful immunosuppression.
            Article 0 comments Cited 336 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The immune modulator FTY720 targets sphingosine 1-phosphate receptors.

              Volker Brinkmann, Michael D Davis, Christopher E. Heise … (2002)
              Immunosuppressant drugs such as cyclosporin have allowed widespread organ transplantation, but their utility remains limited by toxicities, and they are ineffective in chronic management of autoimmune diseases such as multiple sclerosis. In contrast, the immune modulating drug FTY720 is efficacious in a variety of transplant and autoimmune models without inducing a generalized immunosuppressed state and is effective in human kidney transplantation. FTY720 elicits a lymphopenia resulting from a reversible redistribution of lymphocytes from circulation to secondary lymphoid tissues by unknown mechanisms. Using FTY720 and several analogs, we show now that FTY720 is phosphorylated by sphingosine kinase; the phosphorylated compound is a potent agonist at four sphingosine 1-phosphate receptors and represents the therapeutic principle in a rodent model of multiple sclerosis. Our results suggest that FTY720, after phosphorylation, acts through sphingosine 1-phosphate signaling pathways to modulate chemotactic responses and lymphocyte trafficking.
              Article 0 comments Cited 309 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-journal-id): 0376617
                Journal ID (pubmed-jr-id): 5462
                Journal ID (nlm-ta): Lab Invest
                Journal ID (iso-abbrev): Lab. Invest.
                Title: Laboratory investigation; a journal of technical methods and pathology
                ISSN (Print): 0023-6837
                ISSN (Electronic): 1530-0307
                Publication date Nihms-submitted: 24 January 2013
                Publication date (Electronic): 18 February 2013
                Publication date (Print): April 2013
                Publication date PMC-release: 01 October 2013
                Volume: 93
                Issue: 4
                Pages: 462-471
                Affiliations
                [1 ]Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA
                [2 ]Departments of Surgery and Emergency Medicine, Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Boston, MA, USA
                Author notes
                Correspondence to: Teresa Sanchez, PhD, Beth Israel Deaconess Medical Center, 330 Brookline Ave., RN-227A, Boston, MA 02215, USA, tsanchez@ 123456bidmc.harvard.edu or Scott J. Rodig, MD, PhD, 75 Francis St., Department of Pathology, Brigham and Women’s Hospital, Boston, MA, 02115, USA. srodig@ 123456partners.org
                [*]

                co-senior (co-corresponding) authors

                Article
                Manuscript ID: NIHMS435944
                DOI: 10.1038/labinvest.2013.7
                PMC ID: 3612140
                PubMed ID: 23419711
                SO-VID: 6d4fbcf0-25d5-47bd-ab39-81cdd006c489
                License:

                Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                History
                Categories
                Subject: Article

                ScienceOpen disciplines: Pathology
                Keywords: sphingosine-1-phosphate (s1p),s1pr1,classical hodgkin lymphoma,migration,dissemination,fingolimod
                Data availability:
                ScienceOpen disciplines: Pathology
                Keywords: sphingosine-1-phosphate (s1p), s1pr1, classical hodgkin lymphoma, migration, dissemination, fingolimod

                Comments

                Comment on this article

                scite_

                Similar content496

                See all similar

                Cited by16

                See all cited by

                Most referenced authors940

                See all reference authors