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Anti‐human procathepsin D activation peptide antibodies inhibit breast cancer development

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Abstract

Enzymatically inactive procathepsin D secreted from cancer cells has been confirmed to play a role in development of human breast cancer. In the present study, we focused on the role of activation peptide which was in our preliminary studies suggested to be most probably responsible for mitogenic activity of procathepsin D. Using synthetic fragments and antibodies raised against individual fragments, we demonstrated that the growth factor activity of activation peptide is localized in a nine amino acid stretch (AA 36–44) of activation peptide and moreover both anti‐activation peptide and anti‐ 27–44 peptide antibodies administered in vivo inhibited the growth of human breast tumors in athymic nude mice.

Taking into account our previous results and presented data, we hypothesize that the interaction of procathepsin D activation peptide with an unknown surface receptor is mediated by a sequence 36–44 plus close vicinity. We also propose that this interaction leads in certain types of tumor derived cell lines to proliferation and higher motility. Blocking of the interaction of activation peptide by specific antibodies or antagonists might be a valuable tool in breast cancer inhibition.

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Authors and Affiliations

  1. Department of Pathology, School of Medicine, University of Louisville, Louisville, KY‐, USA

    Vaclav Vetvicka & Jana Vetvickova

  2. Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic

    Martin Fusek

Authors
  1. Vaclav Vetvicka
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  2. Jana Vetvickova
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  3. Martin Fusek
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Vetvicka, V., Vetvickova, J. & Fusek, M. Anti‐human procathepsin D activation peptide antibodies inhibit breast cancer development. Breast Cancer Res Treat 57, 261–269 (1999). https://doi.org/10.1023/A:1006238003772

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