Skip to main content

Advertisement

Log in

Regulation of adhesion by vascular endothelial growth factor in HaCaT cells

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Cell adhesion is an important process during morphogenesis, differentiation, and homeostasis in cell biology. The role of vascular endothelial growth factor (VEGF) in cell adhesion of keratinocytes is unclear. In our study, a human keratinocyte cell line, HaCaT cells, which mimics various properties of normal epidermal keratinocytes, was included to elucidate the effect of VEGF on cell–cell adhesion and cell–plate adhesion. Expression of adhesion molecules account for cell adhesion and signal transduction pathways involved in the effect of VEGF on adhesion of HaCaT cells were further investigated. Significant increase of cell–cell adhesion but decrease of the cell–plate adhesion of HaCaT cells induced by VEGF165 was detected. VEGF increases expression of E-cadherin, but inhibits expression of integrin α6β4 subunit. VEGF165 at 100 ng/ml activates extracellular signal-regulated kinase. These changes of cell adhesion induced by VEGF were blocked by ERK and VEGFR-2 inhibitor. Our findings suggest that VEGF may modulate cell adhesion of HaCaT cells partly through activation of VEGFR-2/ERK1/2 signaling pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Yano S, Komine M, Fujimoto M et al (2003) Interleukin 15 induces the signals of epidermal proliferation through ERK and PI 3-kinase in a human epidermal keratinocyte cell line, HaCaT. Biochem Biophys Res Commun 301:841–847

    Article  CAS  PubMed  Google Scholar 

  2. Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9:669–676

    Article  CAS  PubMed  Google Scholar 

  3. Brown LF, Yeo KT, Berse B et al (1992) Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing. J Exp Med 176:1375–1379

    Article  CAS  PubMed  Google Scholar 

  4. Detmar M, Brown LF, Claffey KP et al (1994) Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis. J Exp Med 180:1141–1146

    Article  CAS  PubMed  Google Scholar 

  5. Man XY, Yang XH, Cai SQ et al (2006) Immunolocalization and expression of vascular endothelial growth factor receptors (VEGFRs) and neuropilins (NRPs) on keratinocytes in human epidermis. Mol Med 12:127–136

    Article  CAS  PubMed  Google Scholar 

  6. Yang XH, Man XY, Cai SQ et al (2006) Expression of VEGFR-2 on HaCaT cells is regulated by VEGF and plays an active role in mediating VEGF induced effects. Biochem Biophys Res Commun 349:31–38

    Article  CAS  PubMed  Google Scholar 

  7. Millauer B, Wizigmann-Voos S, Schnürch H et al (1993) High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 72:835–846

    Article  CAS  PubMed  Google Scholar 

  8. van Roy F, Berx G (2008) The cell–cell adhesion molecule E-cadherin. Cell Mol Life Sci 65:3756–3788

    Article  CAS  PubMed  Google Scholar 

  9. Luo BH, Carman CV, Springer TA (2007) Structural basis of integrin regulation and signaling. Annu Rev Immunol 25:619–647

    Article  CAS  PubMed  Google Scholar 

  10. Vogelmann R, Nguyen-Tat MD, Giehl K et al (2005) TGFbeta-induced downregulation of E-cadherin-based cell–cell adhesion depends on PI3-kinase and PTEN. J Cell Sci 118:4901–4912

    Article  CAS  PubMed  Google Scholar 

  11. Chen PN, Chu SC, Chiou HL et al (2006) Mulberry anthocyanins, cyanidin 3-rutinoside and cyanidin 3-glucoside, exhibited an inhibitory effect on the migration and invasion of a human lung cancer cell line. Cancer Lett 235:248–259

    Article  CAS  PubMed  Google Scholar 

  12. Watt FM (2002) Role of integrins in regulating epidermal adhesion growth and differentiation. EMBO J 21:3919–3926

    Article  CAS  PubMed  Google Scholar 

  13. Shen S, Fan J, Cai B et al (2010) Vascular endothelial growth factor enhances cancer cell adhesion to microvascular endothelium in vivo. Exp Physiol 95:369–379

    Article  CAS  PubMed  Google Scholar 

  14. Goebel S, Huang M, Davis WC et al (2006) VEGF-A stimulation of leukocyte adhesion to colonic microvascular endothelium: implications for inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol 290:G648–G654

    Article  CAS  PubMed  Google Scholar 

  15. Kim I, Moon SO, Park SK et al (2001) Angiopoietin-1 reduces VEGF-stimulated leukocyte adhesion to endothelial cells by reducing ICAM-1, VCAM-1, and E-selectin expression. Circ Res 89:477–479

    Article  CAS  PubMed  Google Scholar 

  16. Bouzin C, Brouet A, De Vriese J et al (2007) Effects of vascular endothelial growth factor on the lymphocyte-endothelium interactions: identification of caveolin-1 and nitric oxide as control points of endothelial cell anergy. J Immunol 178:1505–1511

    CAS  PubMed  Google Scholar 

  17. Shiozaki H, Oka H, Inoue M et al (1996) E-cadherin mediated adhesion system in cancer cells. Cancer 77(Suppl 8):1605–1613

    CAS  PubMed  Google Scholar 

  18. Gonzalez-Moreno O, Lecanda J, Green JE et al (2010) VEGF elicits epithelial-mesenchymal transition (EMT) in prostate intraepithelial neoplasia (PIN)-like cells via an autocrine loop. Exp Cell Res 316:554–567

    Article  CAS  PubMed  Google Scholar 

  19. Knies Y, Bernd A, Kaufmann R et al (2006) Mechanical stretch induces clustering of beta1-integrins and facilitates adhesion. Exp Dermatol 15:347–355

    Article  CAS  PubMed  Google Scholar 

  20. Kuwano Y, Fujimoto M, Watanabe R et al (2007) The involvement of Gab1 and PI 3-kinase in beta1 integrin signaling in keratinocytes. Biochem Biophys Res Commun 361:224–229

    Article  CAS  PubMed  Google Scholar 

  21. Nissinen L, Pirila L, Heino J (1997) Bone morphogenetic protein-2 is a regulator of cell adhesion. Exp Cell Res 230:377–385

    Article  CAS  PubMed  Google Scholar 

  22. Zhang L, Koivisto L, Heino J et al (2004) Bacterial heat shock protein 60 may increase epithelial cell migration through activation of MAP kinases and inhibition of alpha6beta4 integrin expression. Biochem Biophys Res Commun 319:1088–1095

    Article  CAS  PubMed  Google Scholar 

  23. Geuijen CA, Sonnenberg A (2002) Dynamics of the alpha6beta4 integrin in keratinocytes. Mol Biol Cell 13:3845–3858

    Article  CAS  PubMed  Google Scholar 

  24. Mercurio AM, Rabinovitz I, Shaw LM (2001) The alpha 6 beta 4 integrin and epithelial cell migration. Curr Opin Cell Biol 13:541–545

    Article  CAS  PubMed  Google Scholar 

  25. Yao YG, Yang HS, Cao Z et al (2005) Upregulation of placental growth factor by vascular endothelial growth factor via a post-transcriptional mechanism. FEBS Lett 579:1227–1234

    Article  CAS  PubMed  Google Scholar 

  26. Berrou E, Bryckaert M (2001) Platelet-derived growth factor inhibits smooth muscle cell adhesion to fibronectin by ERK-dependent and ERK-independent pathways. J Biol Chem 276:39303–39309

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This study was supported by Grants from the National Natural Science Foundation of China (NSFC) (no. 30771945) and the Natural Science Foundation of Zhejiang Province (no. 399126).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Min Zheng.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, C., Man, X., Li, W. et al. Regulation of adhesion by vascular endothelial growth factor in HaCaT cells. Mol Cell Biochem 346, 173–178 (2011). https://doi.org/10.1007/s11010-010-0602-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-010-0602-7

Keywords

Navigation