Home LiteratureArticle Details
PMID: 22448259 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Semaphorin 3A suppresses tumor growth and metastasis in mice melanoma model.

PloS one ·Vol. 7 ·No. 3 ·2012-00-00 ·Pages e33633

Chakraborty G, Kumar S, Mishra R, Patil TV, Kundu GC

Abstract

Recent understanding on cancer therapy indicated that targeting metastatic signature or angiogenic switch could be a promising and rational approach to combat cancer. Advancement in cancer research has demonstrated the potential role of various tumor suppressor proteins in inhibition of cancer progression. Current studies have shown that axonal sprouting inhibitor, semaphorin 3A (Sema 3A) acts as a potent suppressor of tumor angiogenesis in various cancer models. However, the function of Sema 3A in regulation of melanoma progression is not well studied, and yet to be the subject of intense investigation. In this study, using multiple in vitro and in vivo approaches we have demonstrated that Sema 3A acts as a potent tumor suppressor in vitro and in vivo mice (C57BL/6) models. Mouse melanoma (B16F10) cells overexpressed with Sema 3A resulted in significant inhibition of cell motility, invasiveness and proliferation as well as suppression of in vivo tumor growth, angiogenesis and metastasis in mice models. Moreover, we have observed that Sema 3A overexpressed melanoma clone showed increased sensitivity towards curcumin and Dacarbazine, anti-cancer agents. Our results demonstrate, at least in part, the functional approach underlying Sema 3A mediated inhibition of tumorigenesis and angiogenesis and a clear understanding of such a process may facilitate the development of novel therapeutic strategy for the treatment of cancer.

MeSH Terms
Animals Antineoplastic Agents/pharmacology Antineoplastic Agents, Alkylating/pharmacology Apoptosis/drug effects Blotting, Western Case-Control Studies Cell Adhesion/drug effects Cell Movement/drug effects Cell Proliferation/drug effects Cells, Cultured Curcumin/pharmacology Dacarbazine/pharmacology Human Umbilical Vein Endothelial Cells/drug effects Humans Immunoenzyme Techniques Liver Neoplasms/metabolism,prevention & control,secondary Lung Neoplasms/metabolism,prevention & control,secondary Male Melanoma, Experimental/metabolism,pathology,prevention & control Mice Mice, Inbred C57BL Neovascularization, Pathologic/prevention & control Phosphorylation/drug effects RNA, Messenger/genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Semaphorin-3A/genetics,metabolism Wound Healing/drug effects
Chemicals
Antineoplastic Agents Antineoplastic Agents, Alkylating RNA, Messenger Semaphorin-3A Dacarbazine Curcumin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Chakraborty Goutam
National Center for Cell Science (NCCS), NCCS Complex, Pune, India.
Kumar Santosh
Mishra Rosalin
Patil Tushar V
Kundu Gopal C
References (50)
50 references, click to expand
  1. Osteopontin induces nuclear factor kappa B-mediated promatrix metalloproteinase-2 activation through I kappa B alpha /IKK signaling pathways, and curcumin (diferulolylmethane) down-regulates these pathways.
    J Biol Chem. 2003 Apr 18;278(16):14487-97 PMID: 12473670
  2. Serine 15 phosphorylation of p53 directs its interaction with B56gamma and the tumor suppressor activity of B56gamma-specific protein phosphatase 2A.
    Mol Cell Biol. 2008 Jan;28(1):448-56 PMID: 17967874
  3. A novel triterpenoid isolated from the root bark of Ailanthus excelsa Roxb (Tree of Heaven), AECHL-1 as a potential anti-cancer agent.
    PLoS One. 2009;4(4):e5365 PMID: 19399188
  4. Increased class 3 semaphorin expression modulates the invasive and adhesive properties of prostate cancer cells.
    Int J Oncol. 2007 May;30(5):1231-8 PMID: 17390026
  5. Semaphorin 3A is a chemoattractant for cortical apical dendrites.
    Nature. 2000 Apr 6;404(6778):567-73 PMID: 10766232
  6. Angiogenesis in cancer and other diseases.
    Nature. 2000 Sep 14;407(6801):249-57 PMID: 11001068
  7. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor.
    Cell. 1998 Mar 20;92(6):735-45 PMID: 9529250
  8. Class 3 semaphorins control vascular morphogenesis by inhibiting integrin function.
    Nature. 2003 Jul 24;424(6947):391-7 PMID: 12879061
  9. Fighting cancer by attacking its blood supply.
    Sci Am. 1996 Sep;275(3):150-4 PMID: 8701285
  10. Collapsin: a protein in brain that induces the collapse and paralysis of neuronal growth cones.
    Cell. 1993 Oct 22;75(2):217-27 PMID: 8402908
  11. Semaphorins and tumor angiogenesis.
    Angiogenesis. 2009;12(2):187-93 PMID: 19266292
  12. Transcriptional regulation of human osteopontin promoter by histone deacetylase inhibitor, trichostatin A in cervical cancer cells.
    Mol Cancer. 2010 Jul 07;9:178 PMID: 20609221
  13. To move or not to move? Semaphorin signalling in cell migration.
    EMBO Rep. 2004 Apr;5(4):356-61 PMID: 15060572
  14. Semaphorins in cancer.
    Front Biosci. 2005 Jan 01;10:751-60 PMID: 15569615
  15. Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth.
    Cancer Cell. 2007 Jan;11(1):53-67 PMID: 17222790
  16. Parallel progression of primary tumours and metastases.
    Nat Rev Cancer. 2009 Apr;9(4):302-12 PMID: 19308069
  17. Neuropilin is a receptor for the axonal chemorepellent Semaphorin III.
    Cell. 1997 Aug 22;90(4):739-51 PMID: 9288753
  18. Neuropilin-1 mediates collapsin-1/semaphorin III inhibition of endothelial cell motility: functional competition of collapsin-1 and vascular endothelial growth factor-165.
    J Cell Biol. 1999 Jul 12;146(1):233-42 PMID: 10402473
  19. The tumor suppressor semaphorin 3B triggers a prometastatic program mediated by interleukin 8 and the tumor microenvironment.
    J Exp Med. 2008 May 12;205(5):1155-71 PMID: 18458115
  20. Endogenous osteonectin/SPARC/BM-40 expression inhibits MDA-MB-231 breast cancer cell metastasis.
    Cancer Res. 2005 Aug 15;65(16):7370-7 PMID: 16103089
  21. Inhibition of lung cancer cell growth and induction of apoptosis after reexpression of 3p21.3 candidate tumor suppressor gene SEMA3B.
    Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13954-9 PMID: 11717452
  22. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins.
    Cancer Lett. 2008 Oct 8;269(2):199-225 PMID: 18479807
  23. Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors.
    Cell. 1999 Oct 1;99(1):59-69 PMID: 10520994
  24. Role of angiogenesis in tumor growth and metastasis.
    Semin Oncol. 2002 Dec;29(6 Suppl 16):15-8 PMID: 12516034
  25. Melanoma invasion - current knowledge and future directions.
    Pigment Cell Res. 2007 Jun;20(3):161-72 PMID: 17516924
  26. Cyr61 promotes breast tumorigenesis and cancer progression.
    Oncogene. 2002 Nov 21;21(53):8178-85 PMID: 12444554
  27. Human semaphorins A(V) and IV reside in the 3p21.3 small cell lung cancer deletion region and demonstrate distinct expression patterns.
    Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4120-5 PMID: 8633026
  28. VEGF and the quest for tumour angiogenesis factors.
    Nat Rev Cancer. 2002 Oct;2(10):795-803 PMID: 12360282
  29. Disruption of semaphorin III/D gene causes severe abnormality in peripheral nerve projection.
    Neuron. 1997 Sep;19(3):519-30 PMID: 9331345
  30. Differential expression of the semaphorin 3A pathway in prostatic cancer.
    Histopathology. 2009 Oct;55(4):392-8 PMID: 19817889
  31. Semaphorin 3A is an endogenous angiogenesis inhibitor that blocks tumor growth and normalizes tumor vasculature in transgenic mouse models.
    J Clin Invest. 2009 Nov;119(11):3356-72 PMID: 19809158
  32. Signalling by semaphorin receptors: cell guidance and beyond.
    Trends Cell Biol. 2000 Sep;10(9):377-83 PMID: 10932095
  33. Illuminating the metastatic process.
    Nat Rev Cancer. 2007 Oct;7(10):737-49 PMID: 17891189
  34. Distinct 3p21.3 deletions in lung cancer and identification of a new human semaphorin.
    Oncogene. 1996 Mar 21;12(6):1289-97 PMID: 8649831
  35. Competing autocrine pathways involving alternative neuropilin-1 ligands regulate chemotaxis of carcinoma cells.
    Cancer Res. 2003 Sep 1;63(17):5230-3 PMID: 14500350
  36. Cancer statistics, 2010.
    CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300 PMID: 20610543
  37. Hypoxia regulates cross-talk between Syk and Lck leading to breast cancer progression and angiogenesis.
    J Biol Chem. 2006 Apr 21;281(16):11322-31 PMID: 16474166
  38. Targeting endothelial and tumor cells with semaphorins.
    Cancer Metastasis Rev. 2007 Dec;26(3-4):421-31 PMID: 17768598
  39. Growth inhibition of established B16-F10 lung metastases by sequential aerosol delivery of p53 gene and 9-nitrocamptothecin.
    Gene Ther. 2002 Mar;9(5):353-7 PMID: 11938455
  40. Semaphorin 3F gene from human 3p21.3 suppresses tumor formation in nude mice.
    Cancer Res. 2002 May 1;62(9):2637-43 PMID: 11980661
  41. Semaphorin-3F is an inhibitor of tumor angiogenesis.
    Cancer Res. 2004 Feb 1;64(3):1008-15 PMID: 14871832
  42. The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules.
    Cell. 1993 Dec 31;75(7):1389-99 PMID: 8269517
  43. Down-regulation of osteopontin attenuates breast tumour progression in vivo.
    J Cell Mol Med. 2008 Dec;12(6A):2305-18 PMID: 18266970
  44. The role of neuropilin in vascular and tumor biology.
    Adv Exp Med Biol. 2002;515:33-48 PMID: 12613541
  45. Osteopontin promotes vascular endothelial growth factor-dependent breast tumor growth and angiogenesis via autocrine and paracrine mechanisms.
    Cancer Res. 2008 Jan 1;68(1):152-61 PMID: 18172307
  46. Successful inhibition of tumor development by specific class-3 semaphorins is associated with expression of appropriate semaphorin receptors by tumor cells.
    PLoS One. 2008 Sep 26;3(9):e3287 PMID: 18818766
  47. Semaphorin SEMA3F has a repulsing activity on breast cancer cells and inhibits E-cadherin-mediated cell adhesion.
    Neoplasia. 2005 Feb;7(2):180-9 PMID: 15802023
  48. Isolation of the human semaphorin III/F gene (SEMA3F) at chromosome 3p21, a region deleted in lung cancer.
    Genomics. 1996 Feb 15;32(1):39-48 PMID: 8786119
  49. The possible role of angiogenesis in the metastatic potential of human melanoma. Clinicopathological aspects.
    Melanoma Res. 1993 Feb;3(1):5-14 PMID: 7682462
  50. The tumor suppressor p53 transcriptionally regulates cGKI expression during neuronal maturation and is required for cGMP-dependent growth cone collapse.
    J Neurosci. 2009 Dec 2;29(48):15155-60 PMID: 19955367
Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
Published
2012-00-00
Epub
2012-00-20
Pages
e33633
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3308985
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]