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Molecular Cancer
Published in: Molecular Cancer 1/2010

Open Access 01-12-2010 | Review

Roles of Sema4D and Plexin-B1 in tumor progression

Authors: Ewe Seng Ch'ng, Atsushi Kumanogoh

Published in: Molecular Cancer | Issue 1/2010

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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.
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Literature
1.
Goodman CS, Kolodkin AL, Luo Y, Püschel AW, Raper JA: Unified Nomenclature for the Semaphorins/Collapsins. Cell. 1999, 97: 551-552. 10.1016/S0092-8674(00)80766-7CrossRef
2.
Tamagnone L, Artigiani S, Chen H, He Z, Ming G-l, Song H-j, Chedotal A, Winberg ML, Goodman CS, Poo M-m: Plexins Are a Large Family of Receptors for Transmembrane, Secreted, and GPI-Anchored Semaphorins in Vertebrates. Cell. 1999, 99: 71-80. 10.1016/S0092-8674(00)80063-XCrossRefPubMed
3.
4.
Tran TS, Kolodkin AL, Bharadwaj R: Semaphorin Regulation of Cellular Morphology. Annu Rev Cell Dev Biol. 2007, 23: 263-292. 10.1146/annurev.cellbio.22.010605.093554CrossRefPubMed
5.
Mizui M, Kumanogoh A, Kikutani H: Immune Semaphorins: Novel Features of Neural Guidance Molecules. J Clin Immunol. 2009, 29: 1-11. 10.1007/s10875-008-9263-7CrossRefPubMed
6.
Neufeld G, Kessler O: The semaphorins: versatile regulators of tumour progression and tumour angiogenesis. Nat Rev Cancer. 2008, 8: 632-645. 10.1038/nrc2404CrossRefPubMed
7.
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. 10.1242/jcs.030197CrossRefPubMed
8.
Flannery E, Duman-Scheel M: Semaphorins at the interface of development and cancer. Curr Drug Targets. 2009, 10: 611-619.CrossRefPubMed
9.
10.
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.PubMed
11.
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. 10.1073/pnas.93.21.11780PubMedCentralCrossRefPubMed
12.
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. 10.1074/jbc.271.52.33376CrossRefPubMed
13.
Kumanogoh A, Watanabe C, Lee I, Wang X, Shi W, Araki H, Hirata H, Iwahori K, Uchida J, Yasui T: 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. 10.1016/S1074-7613(00)00062-5CrossRefPubMed
14.
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. 10.1093/intimm/dxg098CrossRefPubMed
15.
Kumanogoh A, Suzuki K, Ch'ng E, Watanabe C, Marukawa S, Takegahara N, Ishida I, Sato T, Habu S, Yoshida K: 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.CrossRefPubMed
16.
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.CrossRefPubMed
17.
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. 10.1093/intimm/dxh224CrossRefPubMed
18.
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. 10.1093/intimm/7.1.1CrossRefPubMed
19.
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.PubMed
20.
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.PubMed
21.
Moreau-Fauvarque C, Kumanogoh A, Camand E, Jaillard C, Barbin G, Boquet I, Love C, Jones EY, Kikutani H, Lubetzki C: 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.PubMed
22.
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. 10.1016/S0896-6273(02)00750-XCrossRefPubMed
23.
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. 10.1126/science.1097545CrossRefPubMed
24.
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. 10.1111/j.1365-2443.2004.00766.xCrossRef
25.
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. 10.1083/jcb.200806160PubMedCentralCrossRefPubMed
26.
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. 10.1182/blood-2004-07-2885CrossRefPubMed
27.
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. 10.1158/0008-5472.CAN-04-0126CrossRefPubMed
28.
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. 10.1074/jbc.M705467200CrossRefPubMed
29.
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. 10.1128/MCB.25.16.6889-6898.2005PubMedCentralCrossRefPubMed
30.
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. 10.1002/cncr.22764CrossRefPubMed
31.
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. 10.1073/pnas.0508825103PubMedCentralCrossRefPubMed
32.
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. 10.1074/jbc.M609570200CrossRefPubMed
33.
Sierra JR, Corso S, Caione L, Cepero V, Conrotto P, Cignetti A, Piacibello W, Kumanogoh A, Kikutani H, Comoglio PM: Tumor angiogenesis and progression are enhanced by Sema4D produced by tumor-associated macrophages. J Exp Med. 2008, 205: 1673-1685. 10.1084/jem.20072602PubMedCentralCrossRefPubMed
34.
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- 10.1186/1471-213X-7-55PubMedCentralCrossRefPubMed
35.
Trusolino L, Comoglio PM: Scatter-factor and semaphorin receptors: cell signalling for invasive growth. Nat Rev Cancer. 2002, 2: 289-300. 10.1038/nrc779CrossRefPubMed
36.
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. 10.1038/ncb843CrossRefPubMed
37.
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. 10.1038/sj.onc.1207650CrossRefPubMed
38.
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. 10.1074/jbc.M210156200CrossRefPubMed
39.
Swiercz JM, Worzfeld T, Offermanns S: ErbB-2 and Met Reciprocally Regulate Cellular Signaling via Plexin-B1. J Biol Chem. 2008, 283: 1893-1901. 10.1074/jbc.M706822200CrossRefPubMed
40.
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. 10.1083/jcb.200312094PubMedCentralCrossRefPubMed
41.
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. 10.1083/jcb.200508204PubMedCentralCrossRefPubMed
42.
Wong OG, Nitkunan T, Oinuma I, Zhou C, Blanc V, Brown RS, Bott SR, Nariculam J, Box G, Munson P: Plexin-B1 mutations in prostate cancer. Proc Natl Acad Sci USA. 2007, 104: 19040-19045. 10.1073/pnas.0702544104PubMedCentralCrossRefPubMed
43.
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. 10.1182/blood-2004-10-3873CrossRefPubMed
44.
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. 10.1016/j.ejca.2008.10.016CrossRefPubMed
45.
Rody A, Holtrich U, Gaetje R, Gehrmann M, Engels K, von Minckwitz G, Loibl S, Diallo-Danebrock R, Ruckhaberle E, Metzler D: Poor outcome in estrogen receptor-positive breast cancers predicted by loss of plexin B1. Clin Cancer Res. 2007, 13: 1115-1122. 10.1158/1078-0432.CCR-06-2433CrossRefPubMed
46.
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.CrossRefPubMed
47.
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.PubMed
48.
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. 10.1016/j.str.2007.12.012PubMedCentralCrossRefPubMed
49.
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. 10.1038/onc.2009.133PubMedCentralCrossRefPubMed
Metadata
Title
Roles of Sema4D and Plexin-B1 in tumor progression
Authors
Ewe Seng Ch'ng
Atsushi Kumanogoh
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2010
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-9-251

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