Advertisement

Chinese Journal of Cancer Research

, Volume 10, Issue 2, pp 94–99 | Cite as

Adhesion-induce protein tyrosine phosphory-lation is associated with invasive and metastatic potentials in B16-BL6 melanoma cells

  • Yan Chunhong 
  • Han Rui 
Basic Investigations
  • 16 Downloads

Abstract

Objective: The interaction of cancer cell with extracellular matrix (ECM) happens as an earlier and specific event in the invasive and metastatic cascade. To explore the key element(s) in cancer metastasis and observe the cell-ECM interaction and its role. Methods: To interrupt the cell-ECM interaction by suppression of adhesion-induced protein tyrosine phosphorylation with protein tyrosine kinase inhibitor genistein in B16-B16 mouse melanoma cells. Results: When B16-BL6 cells attached to Matrigel, a solubilized basement membrane preparation from EHS sarcoma, a 125 kDa protein increased its phosphotyrosine content dramatically. In contrast, when the cells were pretreated with 20μM or 30 μM genistein for 3 days, it was revealed a less increase in the phosphotyrosine content of this 125 kDa protein in response to cell attachment to ECM was revealed with immunoblot analysis. Accompanied by the lower level of adhesion-induced protein tyrosine phosphorylation the genistein-treated cells exhibited a decrease in their capabilities of adhesion to Matrigel and invasion through reconstituted basement membrane. The potentials of and forming lung metastatic nodules were also shown to be decreased dramatically in these genistein-treated cells. Conclusion: It was suggested that protein tyrosine phosphorylation in cell-ECM interaction might be associated with invasive and metastatic potentials in cancer cells.

Key words

Adhesion Protein tyrosine phosphorylation Cell-ECM interaction Invasion Metastasis Genistein 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Liotta LA, Steeg PS, Stetler-Stevenson WG, et al. Cancer metastasis and angio-genesis: an imbalance of positive and negative regulation. Cell 1991; 64: 327.PubMedCrossRefGoogle Scholar
  2. 2.
    Stetler-Stevenson WG, Azanvoorian S, Liotta LA, et al. Tumor cell interactions with the extracellular matrix during invasion and metastasis. Annu Rev Cell Biol 1993; 9:541.PubMedCrossRefGoogle Scholar
  3. 3.
    Werb Z, Tremble PM, Behrendtsen O, et al. Signal transduction through the fibronection receptor induces collagenases and stromelysin gene expression. J Cell Biol 1989; 109:877.PubMedCrossRefGoogle Scholar
  4. 4.
    Stack MS, Gray RD, Piozzo SV, et al. Modulation of murine B16-F10 melanoma plasminogen activator production by sythetic peptide derived from the laminin A chain. Cancer Res 1993; 53: 1998.PubMedGoogle Scholar
  5. 5.
    Dedhar S. Integrin mediated signal transduction in oncogenesis: an overview. Cancer Metast Rev 1995; 14: 165.CrossRefGoogle Scholar
  6. 6.
    Clark EA, Brugge JS. Integrins and signal transduction pathways: the road taken. Science 1995; 268: 233.PubMedCrossRefGoogle Scholar
  7. 7.
    Kornberg L, Earp S, Parsons JT, et al. Cell adhesion or integrin clustering increases phosphorylation of a focal adhesion-associated tyrosine kinase. J Biol Chem 1992; 267: 23439.PubMedGoogle Scholar
  8. 8.
    Burridge K, Turner CE, Romer LH, et al. Tyrosine phosphrylation of paxillin and pp125FAK accompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly. J Cell Biol 1992; 119: 893.PubMedCrossRefGoogle Scholar
  9. 9.
    Hanks SK, Calab MB, Harper MC, et al. Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronection. Proc Natl Acad Sci USA 1992; 89: 8487.PubMedCrossRefGoogle Scholar
  10. 10.
    Schaller MD, Borgman CA, Cobb BS, et al. pp125FAK, a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc Natl Acad Sci USA 1992; 89: 5192.PubMedCrossRefGoogle Scholar
  11. 11.
    Guan J-L, Shalloway D. Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation. Nature 1992; 358: 690.PubMedCrossRefGoogle Scholar
  12. 12.
    Weiner TM, Liu ET, Craven RJ, et al. Expression of focal adhesion kinase gene and invasive cancer. Lancet 1993; 342: 1024.PubMedCrossRefGoogle Scholar
  13. 13.
    Owens, LV, Xu L, Craven RJ, et al. Overexpression of the focal adhesion kinase (p125FAK) in invasive human tumors. Cancer Res 1995; 55: 2752.PubMedGoogle Scholar
  14. 14.
    McCune BK, Earp HS. The epidermal growth factor receptor tyrosine kinase in liver epithelial cells: the effect of ligand-dependent changes in cellula location. J Biol Chem 1989; 264:15501.PubMedGoogle Scholar
  15. 15.
    Smith PK, Krohn RI, Hermanson GT, et al. Measurement of protein using bicinchoninic acid. Analyt Biochem 1985; 150:76.PubMedCrossRefGoogle Scholar
  16. 16.
    Hiscox S, Hallett MB, Puntis MCA, et al. Inhibition of cancer cell motility and invasion by interleukin-12. Clin Exp Metastasis 1995; 13: 396.PubMedCrossRefGoogle Scholar
  17. 17.
    Saiki I, Murata J, Wataneve K, et al. Inhibition of tumor cell invasion by ubenimax (bestatin)in vitro. Jpn J Cancer Res 1989; 80:873.PubMedGoogle Scholar
  18. 18.
    Kleiman HK, McGarvey ML, Hassell JR, et al. Basement membrane complexes with biological activity. Biochemistry 1986; 25: 312.CrossRefGoogle Scholar
  19. 19.
    Albini A, Iwamoto Y, Kleinman HK, et al. A rapidin vitro assay for quantitating the invasive potential of tumor cells. Cancer Res 1987; 47: 3239.PubMedGoogle Scholar
  20. 20.
    Zwiller J, Sassone-Corsi P, Kakazu K, et al. Inhibition of PDGF-induced c-jun and c-fos expression by a tyrosine protein kinase inhibitor. Oncogene 1991; 6: 219.PubMedGoogle Scholar

Copyright information

© Chinese Journal Of Cancer Research 1998

Authors and Affiliations

  • Yan Chunhong 
    • 1
  • Han Rui 
    • 1
  1. 1.Department of Pharmacology, Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing

Personalised recommendations