Release of the aspartyl protease cathepsin D is associated with and facilitates human breast cancer cell invasion

Teresa Tedone, Mario Correale, Grazia Barbarossa, Valeria Casavola, Angelo Paradiso, Stephan J. Reshkin

Research output: Contribution to journalArticle

Abstract

Data concerning the hormone sensitivity of the release and role of the aspartyl protease cathepsin D in tumor proliferative and invasive processes have been contradictory. To clarify the mechanisms of its release and role we first studied the contribution of estradiol and stripped serum to the time course and kinetics of cathepsin D release, proliferation, and invasion in parallel in the MCF-7 in vitro breast cancer cell culture model. Both estradiol and stripped serum independently stimulated both proliferation and cathepsin D release. However, die dose-response of estradiol and stripped serum-dependent stimulated release were similar to those for invasion and differed from those for proliferation: cathepsin D release and invasion were first stimulated at a stripped serum concentration more than 10-fold lower than that which initiated proliferation and had half stimulation constants almost 10-fold lower than those for proliferation. These results demonstrate that cathepsin D release is not related in any direct way to proliferation. The effect of the reduction of cathepsin D activity or release on in vitro invasion was also measured: both the inhibition of secreted cathepsin D activity by a specific inhibitor, diazoacetyl-DL-Nle-OMe, and the reduction of cathepsin D release by antisense oligonucleotides against its translation start site reduced cellular in vitro invasion without affecting proliferation. Cathepsin D release and activity are concluded to be directly involved in the process of invasion.-Tedone, T., Correale, M., Barbarossa, G., Casavola, V., Paradiso, A., Reshkin, S. J. Release of the aspartyl protease cathepsin D is associated with and facilitates human breast cancer cell invasion.

Original languageEnglish
Pages (from-to)785-792
Number of pages8
JournalFASEB Journal
Volume11
Issue number10
Publication statusPublished - Aug 1997

Keywords

  • MCF-7
  • Proliferation
  • Protease

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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  • Cite this

    Tedone, T., Correale, M., Barbarossa, G., Casavola, V., Paradiso, A., & Reshkin, S. J. (1997). Release of the aspartyl protease cathepsin D is associated with and facilitates human breast cancer cell invasion. FASEB Journal, 11(10), 785-792.