Roles of Sema4D and Plexin-B1 in tumor progression

Ewe Seng Ch'ng, Atsushi Kumanogoh, Ewe Seng Ch'ng, Atsushi Kumanogoh

Abstract

Sema4D, also known as CD100, is a protein belonging to class IV semaphorin. Its physiologic roles in the immune and nervous systems have been extensively explored. However, the roles of Sema4D have extended beyond these traditionally studied territories. Via interaction with its high affinity receptor Plexin-B1, Sema4D-Plexin-B1 involvement in tumor progression is strongly implied. Here, we critically review and delineate the Sema4D-Plexin-B1 interaction in many facets of tumor progression: tumor angiogenesis, regulation of tumor-associated macrophages and control of invasive growth. We correlate the in vitro and in vivo experimental data with the clinical study outcomes, and present a molecular mechanistic basis accounting for the intriguingly contradicting results from these recent studies.

Figures

Figure 1
Figure 1
Interaction of Sema4D and its receptors. Sema4D interacts with its low and high affinity receptors, CD72 and Plexin-B1, respectively to elicit various physiologic responses as well as oncogenesis.
Figure 2
Figure 2
Sema4D-Plexin-B1 signaling pathways in angiogenesis. Sema4D engages Plexin-B1 to induce angiogenesis and tumor angiogenesis via two independent downstream pathways. Plexin-B2 might also play a redundant role in this aspect.
Figure 3
Figure 3
Control of cellular motility by Sema 4D-Plexin-B1 interation via the coopeative mechanism. Coupled with the Met, Ron or ErbB-2 tyrosine kinase receptor at the cellular membrane surface, Sema4D interacts with Plexin-B1 to control cellular motility and invasive growth via Gab1 or Rho-dependant pathways.
Figure 4
Figure 4
Control of cellular motility by Sema 4D-Plexin-B1 interation via the intrinsic mechanism. Decreased intrinsic GAP activity of Plexin-B1 also leads to preferential signaling through the stimulatory R-Ras and Rho-dependant pathways.

References

    1. Goodman CS, Kolodkin AL, Luo Y, Püschel AW, Raper JA. Unified Nomenclature for the Semaphorins/Collapsins. Cell. 1999;97:551–552. doi: 10.1016/S0092-8674(00)80766-7.
    1. Tamagnone L, Artigiani S, Chen H, He Z, Ming G-l, Song H-j, Chedotal A, Winberg ML, Goodman CS, Poo M-m. et al.Plexins Are a Large Family of Receptors for Transmembrane, Secreted, and GPI-Anchored Semaphorins in Vertebrates. Cell. 1999;99:71–80. doi: 10.1016/S0092-8674(00)80063-X.
    1. Pasterkamp RJ, Giger RJ. Semaphorin function in neural plasticity and disease. Curr Opin Neurobiol. 2009;19:263–274. doi: 10.1016/j.conb.2009.06.001.
    1. Tran TS, Kolodkin AL, Bharadwaj R. Semaphorin Regulation of Cellular Morphology. Annu Rev Cell Dev Biol. 2007;23:263–292. doi: 10.1146/annurev.cellbio.22.010605.093554.
    1. Mizui M, Kumanogoh A, Kikutani H. Immune Semaphorins: Novel Features of Neural Guidance Molecules. J Clin Immunol. 2009;29:1–11. doi: 10.1007/s10875-008-9263-7.
    1. Neufeld G, Kessler O. The semaphorins: versatile regulators of tumour progression and tumour angiogenesis. Nat Rev Cancer. 2008;8:632–645. doi: 10.1038/nrc2404.
    1. Capparuccia L, Tamagnone L. Semaphorin signaling in cancer cells and in cells of the tumor microenvironment - two sides of a coin. J Cell Sci. 2009;122:1723–1736. doi: 10.1242/jcs.030197.
    1. Flannery E, Duman-Scheel M. Semaphorins at the interface of development and cancer. Curr Drug Targets. 2009;10:611–619.
    1. Potiron VA, Roche J, Drabkin HA. Semaphorins and their receptors in lung cancer. Cancer Lett. 2009;273:1–14. doi: 10.1016/j.canlet.2008.05.032.
    1. Bougeret C, Mansur IG, Dastot H, Schmid M, Mahouy G, Bensussan A, Boumsell L. Increased surface expression of a newly identified 150-kDa dimer early after human T lymphocyte activation. J Immunol. 1992;148:318–323.
    1. Hall KT, Boumsell L, Schultze JL, Boussiotis VA, Dorfman DM, Cardoso AA, Bensussan A, Nadler LM, Freeman GJ. Human CD100, a novel leukocyte semaphorin that promotes B-cell aggregation and differentiation. Proc Natl Acad Sci USA. 1996;93:11780–11785. doi: 10.1073/pnas.93.21.11780.
    1. Furuyama T, Inagaki S, Kosugi A, Noda S, Saitoh S-i, Ogata M, Iwahashi Y, Miyazaki N, Hamaoka T, Tohyama M. Identification of a Novel Transmembrane Semaphorin Expressed on Lymphocytes. J Biol Chem. 1996;271:33376–33381. doi: 10.1074/jbc.271.52.33376.
    1. Kumanogoh A, Watanabe C, Lee I, Wang X, Shi W, Araki H, Hirata H, Iwahori K, Uchida J, Yasui T. et al.Identification of CD72 as a Lymphocyte Receptor for the Class IV Semaphorin CD100: A Novel Mechanism for Regulating B Cell Signaling. Immunity. 2000;13:621–631. doi: 10.1016/S1074-7613(00)00062-5.
    1. Ishida I, Kumanogoh A, Suzuki K, Akahani S, Noda K, Kikutani H. Involvement of CD100, a lymphocyte semaphorin, in the activation of the human immune system via CD72: implications for the regulation of immune and inflammatory responses. Int Immunol. 2003;15:1027–1034. doi: 10.1093/intimm/dxg098.
    1. Kumanogoh A, Suzuki K, Ch'ng E, Watanabe C, Marukawa S, Takegahara N, Ishida I, Sato T, Habu S, Yoshida K. et al.Requirement for the lymphocyte semaphorin, CD100, in the induction of antigen-specific T cells and the maturation of dendritic cells. J Immunol. 2002;169:1175–1181.
    1. Delaire S, Billard C, Tordjman R, Chedotal A, Elhabazi A, Bensussan A, Boumsell L. Biological Activity of Soluble CD100. II. Soluble CD100, Similarly to H-SemaIII, Inhibits Immune Cell Migration. J Immunol. 2001;166:4348–4354.
    1. Chabbert-de Ponnat I, Marie-Cardine A, Pasterkamp RJ, Schiavon V, Tamagnone L, Thomasset N, Bensussan A, Boumsell L. Soluble CD100 functions on human monocytes and immature dendritic cells require plexin C1 and plexin B1, respectively. Int Immunol. 2005;17:439–447. doi: 10.1093/intimm/dxh224.
    1. Herold C, Bismuth G, Bensussan A, Boumsell L. Activation signals are delivered through two distinct epitopes of CD100, a unique 150 kDa human lymphocyte surface structure previously defined by BB18 mAb. Int Immunol. 1995;7:1–8. doi: 10.1093/intimm/7.1.1.
    1. Herold C, Elhabazi A, Bismuth G, Bensussan A, Boumsell L. CD100 is associated with CD45 at the surface of human T lymphocytes. Role in T cell homotypic adhesion. J Immunol. 1996;157:5262–5268.
    1. Billard C, Delaire S, Raffoux E, Bensussan A, Boumsell L. Switch in the protein tyrosine phosphatase associated with human CD100 semaphorin at terminal B-cell differentiation stage. Blood. 2000;95:965–972.
    1. Moreau-Fauvarque C, Kumanogoh A, Camand E, Jaillard C, Barbin G, Boquet I, Love C, Jones EY, Kikutani H, Lubetzki C. et al.The Transmembrane Semaphorin Sema4D/CD100, an Inhibitor of Axonal Growth, Is Expressed on Oligodendrocytes and Upregulated after CNS Lesion. J Neurosci. 2003;23:9229–9239.
    1. Swiercz JM, Kuner R, Behrens J, Offermanns S. Plexin-B1 Directly Interacts with PDZ-RhoGEF/LARG to Regulate RhoA and Growth Cone Morphology. Neuron. 2002;35:51–63. doi: 10.1016/S0896-6273(02)00750-X.
    1. Oinuma I, Ishikawa Y, Katoh H, Negishi M. The Semaphorin 4D receptor Plexin-B1 is a GTPase activating protein for R-Ras. Science. 2004;305:862–865. doi: 10.1126/science.1097545.
    1. Kenta M, Tatsuo F, Mizue T, Shiho F, Hitomi K, Shinobu I. Sema4D stimulates axonal outgrowth of embryonic DRG sensory neurones. Genes Cells. 2004;9:821–829. doi: 10.1111/j.1365-2443.2004.00766.x.
    1. Giacobini P, Messina A, Morello F, Ferraris N, Corso S, Penachioni J, Giordano S, Tamagnone L, Fasolo A. Semaphorin 4D regulates gonadotropin hormone-releasing hormone-1 neuronal migration through PlexinB1-Met complex. J Cell Biol. 2008;183:555–566. doi: 10.1083/jcb.200806160.
    1. Conrotto P, Valdembri D, Corso S, Serini G, Tamagnone L, Comoglio PM, Bussolino F, Giordano S. Sema4D induces angiogenesis through Met recruitment by Plexin B1. Blood. 2005;105:4321–4329. doi: 10.1182/blood-2004-07-2885.
    1. Basile JR, Barac A, Zhu T, Guan K-L, Gutkind JS. Class IV Semaphorins Promote Angiogenesis by Stimulating Rho-Initiated Pathways through Plexin-B. Cancer Res. 2004;64:5212–5224. doi: 10.1158/0008-5472.CAN-04-0126.
    1. Basile JR, Gavard J, Gutkind JS. Plexin-B1 Utilizes RhoA and Rho Kinase to Promote the Integrin-dependent Activation of Akt and ERK and Endothelial Cell Motility. J Biol Chem. 2007;282:34888–34895. doi: 10.1074/jbc.M705467200.
    1. Basile JR, Afkhami T, Gutkind JS. Semaphorin 4D/Plexin-B1 Induces Endothelial Cell Migration through the Activation of PYK2, Src, and the Phosphatidylinositol 3-Kinase-Akt Pathway. Mol Cell Biol. 2005;25:6889–6898. doi: 10.1128/MCB.25.16.6889-6898.2005.
    1. Ch'ng E, Tomita Y, Zhang B, He J, Hoshida Y, Qiu Y, Morii E, Nakamichi I, Hamada K, Ueda T, Aozasa K. Prognostic significance of CD100 expression in soft tissue sarcoma. Cancer. 2007;110:164–172. doi: 10.1002/cncr.22764.
    1. Basile JR, Castilho RM, Williams VP, Gutkind JS. Semaphorin 4D provides a link between axon guidance processes and tumor-induced angiogenesis. Proc Natl Acad Sci USA. 2006;103:9017–9022. doi: 10.1073/pnas.0508825103.
    1. Basile JR, Holmbeck K, Bugge TH, Gutkind JS. MT1-MMP Controls Tumor-induced Angiogenesis through the Release of Semaphorin 4D. J Biol Chem. 2007;282:6899–6905. doi: 10.1074/jbc.M609570200.
    1. Sierra JR, Corso S, Caione L, Cepero V, Conrotto P, Cignetti A, Piacibello W, Kumanogoh A, Kikutani H, Comoglio PM. et al.Tumor angiogenesis and progression are enhanced by Sema4D produced by tumor-associated macrophages. J Exp Med. 2008;205:1673–1685. doi: 10.1084/jem.20072602.
    1. Fazzari P, Penachioni J, Gianola S, Rossi F, Eickholt B, Maina F, Alexopoulou L, Sottile A, Comoglio P, Flavell R, Tamagnone L. Plexin-B1 plays a redundant role during mouse development and in tumour angiogenesis. BMC Dev Biol. 2007;7:55. doi: 10.1186/1471-213X-7-55.
    1. Trusolino L, Comoglio PM. Scatter-factor and semaphorin receptors: cell signalling for invasive growth. Nat Rev Cancer. 2002;2:289–300. doi: 10.1038/nrc779.
    1. Giordano S, Corso S, Conrotto P, Artigiani S, Gilestro G, Barberis D, Tamagnone L, Comoglio PM. The Semaphorin 4D receptor controls invasive growth by coupling with Met. Nat Cell Biol. 2002;4:720–724. doi: 10.1038/ncb843.
    1. Conrotto P, Corso S, Gamberini S, Comoglio PM, Giordano S. Interplay between scatter factor receptors and B plexins controls invasive growth. Oncogene. 2004;23:5131–5137. doi: 10.1038/sj.onc.1207650.
    1. Artigiani S, Barberis D, Fazzari P, Longati P, Angelini P, van de Loo J-W, Comoglio PM, Tamagnone L. Functional Regulation of Semaphorin Receptors by Proprotein Convertases. J Biol Chem. 2003;278:10094–10101. doi: 10.1074/jbc.M210156200.
    1. Swiercz JM, Worzfeld T, Offermanns S. ErbB-2 and Met Reciprocally Regulate Cellular Signaling via Plexin-B1. J Biol Chem. 2008;283:1893–1901. doi: 10.1074/jbc.M706822200.
    1. Swiercz JM, Kuner R, Offermanns S. Plexin-B1/RhoGEF-mediated RhoA activation involves the receptor tyrosine kinase ErbB-2. J Cell Biol. 2004;165:869–880. doi: 10.1083/jcb.200312094.
    1. Oinuma I, Katoh H, Negishi M. Semaphorin 4D/Plexin-B1-mediated R-Ras GAP activity inhibits cell migration by regulating β1 integrin activity. J Cell Biol. 2006;173:601–613. doi: 10.1083/jcb.200508204.
    1. Wong OG, Nitkunan T, Oinuma I, Zhou C, Blanc V, Brown RS, Bott SR, Nariculam J, Box G, Munson P. et al.Plexin-B1 mutations in prostate cancer. Proc Natl Acad Sci USA. 2007;104:19040–19045. doi: 10.1073/pnas.0702544104.
    1. Deaglio S, Vaisitti T, Bergui L, Bonello L, Horenstein AL, Tamagnone L, Boumsell L, Malavasi F. CD38 and CD100 lead a network of surface receptors relaying positive signals for B-CLL growth and survival. Blood. 2005;105:3042–3050. doi: 10.1182/blood-2004-10-3873.
    1. Rody A, Karn T, Ruckhaberle E, Hanker L, Metzler D, Muller V, Solbach C, Ahr A, Gatje R, Holtrich U, Kaufmann M. Loss of Plexin B1 is highly prognostic in low proliferating ER positive breast cancers--results of a large scale microarray analysis. Eur J Cancer. 2009;45:405–413. doi: 10.1016/j.ejca.2008.10.016.
    1. Rody A, Holtrich U, Gaetje R, Gehrmann M, Engels K, von Minckwitz G, Loibl S, Diallo-Danebrock R, Ruckhaberle E, Metzler D. et al.Poor outcome in estrogen receptor-positive breast cancers predicted by loss of plexin B1. Clin Cancer Res. 2007;13:1115–1122. doi: 10.1158/1078-0432.CCR-06-2433.
    1. Gomez Roman JJ, Garay GO, Saenz P, Escuredo K, Sanz Ibayondo C, Gutkind S, Junquera C, Simon L, Martinez A, Fernandez Luna JL, Val-Bernal JF. Plexin B1 is downregulated in renal cell carcinomas and modulates cell growth. Transl Res. 2008;151:134–140.
    1. Valente G, Nicotra G, Arrondini M, Castino R, Capparuccia L, Prat M, Kerim S, Tamagnone L, Isidoro C. Co-expression of plexin-B1 and Met in human breast and ovary tumours enhances the risk of progression. Cell Oncol. 2009;31:423–436.
    1. Tong Y, Hota PK, Hamaneh MB, Buck M. Insights into Oncogenic Mutations of Plexin-B1 Based on the Solution Structure of the Rho GTPase Binding Domain. Structure. 2008;16:246–258. doi: 10.1016/j.str.2007.12.012.
    1. Argast GM, Croy CH, Couts KL, Zhang Z, Litman E, Chan DC, Ahn NG. Plexin B1 is repressed by oncogenic B-Raf signaling and functions as a tumor suppressor in melanoma cells. Oncogene. 2009;28:2697–2709. doi: 10.1038/onc.2009.133.

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