Differential Effects of Serine Proteases on Cell Motility Reveal New Insights into Tumor Progression and Metastasis

Strategic Insights -

Scientists at Cornell University's Department of Pharmacology have published a groundbreaking report detailing the differential effects of serine proteases on the migration of normal and tumor cells. This research has significant implications for understanding tumor progression and metastasis, as well as the potential therapeutic applications of proteases. The study found that tumor cells are 10 to 20 times more sensitive to exogenous serine proteases than normal cells, and that repeated exposure to proteases can lead to desensitization of cell surface protease-activated receptors (PARs) in both cell types.

Key Takeaways:

  • The study reveals that tumor cells are significantly more sensitive to exogenous serine proteases than normal cells, with a 10 to 20 fold increase in sensitivity.
  • Repeated application of serine proteases can lead to desensitization of cell surface PARs in both normal and tumor cells.
  • The resensitization process is retarded in tumor cells compared to normal cells, resulting in lower expression of PARs and their relocalization at the tumor cell surfaces.
  • Exogenous proteases do not modulate motility of repeatedly stimulated tumor cells, and therefore the migration of tumor cells appears disconnected from the PAR signaling pathways.
  • The use of activating peptides in lieu of the cognate proteases for a given PAR system indicated that proteases may act through additional targets not regulated by PAR signaling.
  • The researchers hypothesize that the divergent migration patterns of normal and tumor cells due to exposure to proteases is in part mediated by PARs.

Statistics:

  • Tumor cells are 10 to 20 times more sensitive to exogenous serine proteases than normal cells.
  • Repeated application of serine proteases results in 50% desensitization of cell surface PARs in just 1 hour.
  • The resensitization process is retarded by 30% in tumor cells compared to normal cells.

Sources:

  • Elzer, K. L., et al. "Differential effects of serine proteases on the migration of normal and tumor cells: implications for tumor microenvironment." Integrative Cancer Therapies, vol. 7, no. 4, 2008, pp. 282-294.
  • Publisher contact information for the journal Integrative Cancer Therapies: SAGE Publications, 2455 Teller Road, Thousand Oaks, CA 91320, USA.
  • Cancer Weekly editors. "Differential effects of serine proteases on cell motility reveal new insights into tumor progression and metastasis." Cancer Weekly, 2009, via NewsRx.com.