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01-08-2010 | Preclinical study

A unique proteolytic fragment of alpha1-antitrypsin is elevated in ductal fluid of breast cancer patient

Authors: Junma Zhou, Bruce Trock, Theodore N. Tsangaris, Neil B. Friedman, Deanna Shapiro, Michelle Brotzman, Yee Chan-Li, Daniel W. Chan, Jinong Li

Published in: Breast Cancer Research and Treatment | Issue 1/2010

Abstract

By comparison of mass spectra from a small cohort of nipple aspiration fluids (NAF), we previously discovered a panel of five candidate breast cancer biomarkers among them an unidentified 4.7 kD peptide BF5. The purposes of the present study were to verify the presence of BF5 in an independent cohort; to determine the protein identity of BF5; and to provide insight into the biology of BF5 production and elevation in tumor-associated NAF. We prospectively collected bilaterally matched NAF from patients with unilateral Stage I/II breast cancer (IBC-31), ductal carcinoma in situ (DCIS-6), atypical ductal hyperplasia (ADH-5), and presumed healthy women who came to routine mammography and had a normal exam (31). Following the consolidation of its cancer-associated expression on SELDI-mass spectrometry, BF5 was isolated by gel electrophoresis and sequenced by tandem mass spectrometry. BF5 was elevated in 15–25% of women with IBC, DCIS, or ADH vs. 0% of controls. This elevation was restricted to the affected breasts. BF5 was identified as 41/42-aa C-terminal peptide of alpha1-antitrypsin (AAT), the principle inhibitor of serine protease neutrophile elastase. The full length AAT showed a consistent expression pattern as C-41/42, and C-41/42 can be generated in vitro by MMP-7 cleavage. In conclusion, elevated C-41/42 is likely the result of elevated AAT synthesis, and the activity of specific MMPs present within the tumor. As other C-terminal fragments of AAT are reported to function as tumor-derived suppressors to the host immune-system, elevated C-41/42 may also be predictive of a poor outcome.

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Title: A unique proteolytic fragment of alpha1-antitrypsin is elevated in ductal fluid of breast cancer patient
Authors: Junma Zhou
Bruce Trock
Theodore N. Tsangaris
Neil B. Friedman
Deanna Shapiro
Michelle Brotzman
Yee Chan-Li
Daniel W. Chan
Jinong Li
Publication date: 01-08-2010
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 1/2010
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-009-0625-5

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