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Cathepsin D: A protease involved in breast cancer metastasis

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Summary

Cathepsin D is an acidic lysosomal protease present in all cells. In estrogen receptor positive and negative breast cancer cell lines, the mRNA coding for pro-cathepsin D is overexpressed and sorting and maturation of the pro-enzyme are altered, via possibly saturation of the Man-6-P/IGF-II receptor, leading to accumulation of the active proteinase in large endosomes and to secretion of the precursor (52K protein). In MCF7 cells, the cathepsin D mRNA is induced directly and transcriptionally by estrogens and indirectly by growth factors. In patients, there is a significant correlation between high cathepsin D concentrations in the cytosol of primary breast cancer and development of metastasis. This marker is independent of other prognostic factors and appears to be particularly useful in axillary node-negative tumors. Transfection of a human cDNA cathepsin D expression vector under the control of SV40 promoter increases the metastatic potential of 3YA1-Ad12 rat tumorigenic cells when intravenously injected into nude mice. The mechanism of cathepsin D-induced metastasis is currently unknown. These results indicate that overexpression of cathepsin D might facilitate breast cancer metastasis, suggesting new possible therapeutic approaches.

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  1. Unité Hormones et Cancer (U 148) INSERM, University of Montpellier 1, 60, rue de Navacelles, 34090, Montpellier, France

    Henri Rochefort, Françoise Capony & Marcel Garcia

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  1. Henri Rochefort
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  2. Françoise Capony
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  3. Marcel Garcia
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Rochefort, H., Capony, F. & Garcia, M. Cathepsin D: A protease involved in breast cancer metastasis. Cancer Metast Rev 9, 321–331 (1990). https://doi.org/10.1007/BF00049522

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