Reevaluating cathepsin D as a biomarker for breast cancer: serum activity levels versus histopathology.

Abstract

Cathepsin D is a lysosomal hydrolase involved in intra- and extracellular proteolysis. This enzyme is aberrantly produced and processed in malignancy, and most notably is over-secreted into the tumor cell microenvironment. This hyper-secretion may lead to excessive degradation of the extracellular matrix, and contribute to tumor progression and metastases. These phenomena have been established in vitro, and there is evidence that Cathepsin D is similarly dysregulated in human breast cancer patients. Because breast cancer lacks an effective screening or surveillance biomarker, here we address the hypothesis that serum Cathepsin D activity may be useful to assess the presence or progression of breast cancer in females. While representative histologic sections from various disease-specific cohorts confirm previous findings that increased Cathepsin D production and secretion correlate with tumor progression, we report no difference in serum Cathepsin D activity between patients who are disease free, patients with pre-invasive or limited invasive disease, and patients with metastatic disease. Furthermore, in patients with known metastatic disease, there were no clinical variables associated with significantly different serum Cathepsin D activity. However, the immunohistochemical localization of Cathepsin D expression in histopathologic sections from breast cancer patients correlates with disease progression. Based on the serum results, and in contradistinction to Cathepsin D localization in breast cancer tissues, our findings support using Cathepsin D as a reliable histopathology biomarker for disease progression, but not for serum screening.

• Authors: Daniel E Abbott, Naira V Margaryan, Jacqueline S Jeruss, Seema Khan, Virginia Kaklamani, David J Winchester, Nora Hansen, Alfred Rademaker, Zhila Khalkhali-Ellis, Mary J C Hendrix
• Journal: Cancer biology & therapy (Cancer Biol Ther) Vol. 9 Issue 1 Pg. 23-30 (Jan 2010) ISSN: 1555-8576 [Electronic] United States
• PMID: 19923884 (Publication Type: Evaluation Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Biomarkers, Tumor
• Cathepsin D

Topics

• Biomarkers, Tumor (metabolism)
• Breast Neoplasms (enzymology, metabolism, pathology)
• Case-Control Studies
• Cathepsin D (metabolism)
• Disease Progression
• Extracellular Matrix (metabolism)
• Female
• Humans
• Lymphatic Metastasis (pathology)
• Lysosomes (enzymology)
• Middle Aged