[Anti-metastatic effects of serine protease inhibitors: animal models for analysis]

Hamostaseologie. 2007 Feb;27(1):64-70.
[Article in German]


To date, no effective adjuvant drug preventing the aggressive spread of tumour cells in late stages of cancer disease or at the time-point of primary tumour removal is available. Although proteases, including members of the large serine protease family, were shown to be promising targets for an anti-metastatic cancer therapy, synthetic protease inhibitors (SPIs) have so far failed to be introduced into the clinic. In addition to considerations in the design of classical in vivo -tests of SPIs as cancer therapy agents, we here review our findings with a straightforward, highly sensitive and very fast in vivo metastasis model and its implications in the development of efficient anti-metastatic SPIs. The lacZ-tagging of tumour cells of this very aggressive T-cell lymphoma model allowed highly sensitive and reproducible detection of metastases within seven days after tumour cell inoculation by X-gal staining of whole organs, allowing cost-effective and material-saving side-by-side screening of a series of SPIs with different specificities for different serine proteases. By establishment of specificity/antimetastatic efficacy correlations we identified coagulation factor Xa as one important target of anti-metastatic SPIs and could use this information for the subsequent design and optimization of factor Xa-specific lead structures.

Conclusion: We exemplify the usefulness of high-throughput in vivo analysis to direct optimization of lead structures and how this may allow unexpected insight into the molecular biology of metastasis.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Humans
  • Neoplasm Metastasis / prevention & control*
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / pathology
  • Serine Proteinase Inhibitors / therapeutic use*


  • Serine Proteinase Inhibitors