The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
권호 표지

Netrin-1 Specifically Enhances Cell Spreading on Fibronectin in Human Glioblastoma Cells

  • Lee, Hyun-Kyoung (Department of Physiology, Medical Science Research Institute, College of Medicine, Dong-A University) ;
  • Seo, In-Ae (Department of Physiology, Medical Science Research Institute, College of Medicine, Dong-A University) ;
  • Shin, Yoon-Kyung (Department of Physiology, Medical Science Research Institute, College of Medicine, Dong-A University) ;
  • Lee, Sang-Hwa (Department of Microbiology, Medical Science Research Institute, College of Medicine, Dong-A University) ;
  • Seo, Su-Young (Department of Microbiology, Medical Science Research Institute, College of Medicine, Dong-A University) ;
  • Suh, Duk-Joon (Department of Physiology, Medical Science Research Institute, College of Medicine, Dong-A University) ;
  • Park, Hwan-Tae (Department of Physiology, Medical Science Research Institute, College of Medicine, Dong-A University)
  • Published : 2008.10.31
Download PDF
⟨ Previous Next ⟩

Abstract

Netrins are secreted molecules and involved in axon guidance, cell migration and tumor development. Recent studies revealed that netrins perform novel functions in such processes as epithelial development and angiogenesis without operating through the classical netrin receptors, DCC (Deleted in Colorectal Cancer) and Unc5h. In the present study, we investigated the roles of netrin-1 and its receptors in cell spreading of human glioblastoma cells, and found that netrin-1 haptotactically enhanced fibronectin-induced cell spreading and focal adhesion formation in U373 glioblastoma cells. Netrin-1 binding to the U373 cell membrane was blocked by an antibody against ${\alpha}v$ integrin subunit, but not by an anti-DCC or anti-Unc5h antibody. In addition, enhancement of the fibronectin response by netrin-1 was abrogated by a function blocking antibody against integrin ${\alpha}v{\beta}3$. Since the ${\alpha}v$ subunit of the integrin family plays an important role in the pathophysiological aspects of cell migration, including tumor angiogenesis and metastasis, our data provide important insight into the molecular mechanism of netrin function.

Keywords

References

  1. Barry ST, Critchley DR. The RhoA-dependent assembly of focal adhesions in Swiss 3T3 cells is associated with increased tyrosine phosphorylation and the recruitment of both pp125FAK and protein kinase C-delta to focal adhesions. J Cell Sci 107: 2033−2045, 1994
  2. Cirulli V, Yebra M. Netrins: beyond the brain. Nat Rev Mol Cell Bio 8: 296−306, 2007
  3. Colamarino SA, Tessier-Lavigne M. The axonal chemoattractant netrin-1 is also a chemorepellent for trochlear motor axons. Cell 81: 621−629, 1995
  4. Danen EH, Yamada KM. Fibronectin, integrins, and growth control. J Cell Physiol 189: 1−13, 2001 https://doi.org/10.1002/jcp.1137
  5. Eliceiri BP, Cheresh DA. Role of alpha v integrins during angiogenesis. Cancer J 3: S245−249, 2000
  6. Hong K, Hinck L, Nishiyama M, Poo MM, Tessier-Lavigne M, Stein E. A ligand gated association between cytoplasmic domains of UNC5 and DCC family receptors converts netrin-induced growth cone attraction to repulsion. Cell 97: 927−941, 1999
  7. Keino-Masu K, Masu M, Hinck L, Leonardo ED, Chan SS, Culotti JG, Tessier-Lavigne M. Deleted in Colorectal Cancer (DCC) encodes a netrin receptor. Cell 87: 175−185, 1996
  8. Kennedy TE, Serafini T, dela Torre JR, Tessier-Lavigne M. Netrins are diffusible chemotropic factors for commissural axons in the embryonic spinal cord. Cell 78: 425−435, 1994
  9. Kim TH, Lee HK, Seo IA, Bae HR, Suh DJ, Wu J, Rao Y, Hwang KG, Park HT. Netrin induces down-regulation of its receptor, Deleted in Colorectal Cancer, through the ubiquitin-proteasome pathway in the embryonic cortical neuron. J Neurochem 95: 1−8, 2005
  10. Lee HK, Seo IA, Park HK, Park HT. Identification of the basement membrane protein nidogen as a candidate ligand for tumor endothelial marker 7 in vitro and in vivo. FEBS Lett 580: 2253−2257, 2006 https://doi.org/10.1016/j.febslet.2006.03.001
  11. Leonardo ED, Hinck L, Masu M, Keino-Masu K, Ackerman SL, Tessier-Lavigne M. Vertebrate homologues of C. elegans UNC-5 are candidate netrin receptors. Nature 386: 833−838, 1997
  12. Liu G, Beggs H, Jürgensen C, Park HT, Tang H, Gorski J, Jones KR, Reichardt LF, Wu J, Rao Y. Netrin requires focal adhesion kinase and Src family kinases for axon outgrowth and attraction. Nat Neurosci 7: 1222−1232, 2004
  13. Ly NP, Komatsuzaki K, Fraser IP, Tseng AA, Prodhan P, Moore KJ, Kinane TB. Netrin-1 inhibits leukocyte migration in vitro and in vivo. Proc Natl Acad Sci USA 102: 14729−14734, 2005
  14. Park HT, Wu J, Rao Y. Molecular control of neuronal migration. Bioessays 24: 821−827, 2002
  15. Park KW, Crouse D, Lee M, Karnik SK, Sorensen LK, Murphy KJ, Kuo CJ, Li DY. The axonal attractant Netrin-1 is an angiogenic factor. Proc Natl Acad Sci USA 101: 16210−16215, 2004
  16. Rodrigues S, De Wever O, Bruyneel E, Rooney RJ, Gespach C. Opposing roles of netrin-1 and the dependence receptor DCC in cancer cell invasion, tumor growth and metastasis. Oncogene 26: 5615−5625, 2007
  17. Schneiders FI, Maertens B, Böse K, Li Y, Brunken WJ, Paulsson M, Smyth N, Koch M. Binding of netrin-4 to laminin short arms regulates basement membrane assembly. J Biol Chem 282: 23750−23758, 2007
  18. Serafini T, Kennedy TE, Galko MJ, Mirzayan C, Jessell TM, Tessier- Lavigne M. The netrins define a family of axon outgrowth- promoting proteins homologous to C. elegans UNC-6. Cell 78: 409−424, 1994
  19. Serini G, Valdembri D, Bussolino F. Integrins and angiogenesis: a sticky business. Exp Cell Res 312: 651−658, 2006
  20. Wheeler AP, Ridley AJ. RhoB affects macrophage adhesion, integrin expression and migration. Exp Cell Res. 313: 3505−3516, 2007
  21. Wilson BD, Ii M, Park KW, Suli A, Sorensen LK, Larrieu-Lahargue F, Urness LD, Suh W, Asai J, Kock GA, Thorne T, Silver M, Thomas KR, Chien CB, Losordo DW, Li DY. Netrins promote developmental and therapeutic angiogenesis. Science 313: 640−644, 2006
  22. Yebra M, Montgomery AM, Diaferia GR, Kaido T, Silletti S, Perez B, Just ML, Hildbrand S, Hurford R, Florkiewicz E, Tessier- Lavigne M, Cirulli V. Recognition of the neural chemoattractant Netrin-1 by integrins alpha6beta4 and alpha3beta1 regulates epithelial cell adhesion and migration. Dev Cell 5: 695−707, 2003