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Cathepsin B and D are localized at the surface of human breast cancer cells

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Pathology & Oncology Research

Abstract

Alterations in trafficking of cathepsins B and D have been reported in human and animal tumors. In MCF-10 human breast epithelial cells, altered trafficking of cathepsin B occurs during their progression from a preneoplastic to neoplastic state. We now show that this is also the case for altered trafficking of cathepsin D. Nevertheless, the two cathepsins are not necessarily trafficked to the same vesicles. Perinuclear vesicles of immortal MCF-10A cells label for both cathepsins B and D, yet the peripheral vesicles found inras-transfected MCF-10AneoT cells label for cathepsin B, cathepsin D or both enzymes. Studies at the electron microscopic level confirm these findings and show in addition surface labeling for both enzymes in the transfected cells. By immunofluorescence staining, cathepsin B can be localized on the outer surface of the cells. Similar patterns of peripheral intracellular and surface staining for cathepsin B are seen in the human breast carcinoma lines MCF-7 and BT20. We suggest that the altered trafficking of cathepsins B and D may be of functional significance in malignant progression of human breast epithelial cells. Translocation of vesicles containing cathepsins B and D toward the cell periphery occurs in human breast epithelial cells that are at the point of transition between the pre-neoplastic and neoplastic state and remains part of the malignant phenotype of breast carcinoma cells.

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Abbreviations

BSA:

bovine serum albumin

HEPES:

N-2-hydroxyethyl-piperazine-N-2-ethanesulfonic acid

IgG:

immunoglobulin G

IgY:

immunoglobulin Y

MPR:

mannose 6-phosphate receptor

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Authors and Affiliations

  1. Department of Pharmacology, Wayne State University, Detroit, USA

    Mansoureh Sameni, Grace Ziegler & Bonnie F. Sloane

  2. Department of Biochemistry, University of Natal, Pietermaritzburg, South Africa

    Edith Elliott, Philip H. Fortgens & Clive Dennison

Authors
  1. Mansoureh Sameni
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  2. Edith Elliott
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  3. Grace Ziegler
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  4. Philip H. Fortgens
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  5. Clive Dennison
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  6. Bonnie F. Sloane
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Corresponding author

Correspondence to Bonnie F. Sloane.

Additional information

The work at Wayne State University was supported by U.S. Public-Health Service Grant CA 56586. Development and maintenance of the MCF-10 human breast epithelial cell lines has been supported by a grant from the Elsa U. Pardee foundation and the core support grant of the Karmanos Cancer Institute. The work at University of Natal was supported by grants from the Research Fund of the University of Natal, the South African Foundation for Research Development and the National Cancer Association of South Africa.

The Confocal Imaging Cora was supported by the Center for Molecular and Cellular Toxicology with Human Application and the Karmanos Cancer Institute.

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Sameni, M., Elliott, E., Ziegler, G. et al. Cathepsin B and D are localized at the surface of human breast cancer cells. Pathol. Oncol. Res. 1, 43–53 (1995). https://doi.org/10.1007/BF02893583

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  • DOI: https://doi.org/10.1007/BF02893583

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