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Immunological and pathobiological roles of fibulin-1 in breast cancer
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Immunological and pathobiological roles of fibulin-1 in breast cancer
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Journal Article
Immunological and pathobiological roles of fibulin-1 in breast cancer
2004
Overview
Fibulin-1 (Fbln-1) is an immunogenic breast cancer-related glycoprotein identified by serological analysis of cDNA expression library (SEREX) strategy. Here, we show that dendritic cells from two breast cancer patients elicited a CD4
+
-mediated T-cell response to Fbln-1 presentation. In both patients, an antibody response to Fbln-1 was also found. By contrast, a Fbln-1-seronegative patient and a weakly seropositive patient demonstrated no such T-cell response. Analysis of human breast cancers for Fbln-1 RNA and protein expression revealed the presence of Fbln-1C and -1D variants. Fbln-1 was detected in the cytoplasm and at the cell surface of different human breast carcinoma cell lines. Immunohistochemical analysis of 528 archival primary breast carcinomas showed the expression of Fbln-1 in 35% of the cases. When the immunohistochemical findings were compared against pathobiological information associated with each specimen, an inverse relationship between Fbln-1 and cathepsin D expression was observed (
P
=0.04). Furthermore, even though long-term survival was similar between Fbln-1-positive and -negative cases, the survival of Fbln-1-positive cases improved when a lymphoid infiltrate was present at the tumour site. Taken together, our findings of an Fbln-1-specific immunity and the improved survival associated with Fbln-1 expression in the presence of lymphoid infiltration point to a role of Fbln-1 in tumour immunosurveillance.
Publisher
Nature Publishing Group UK,Nature Publishing,Nature Publishing Group
Subject
Antibodies, Monoclonal - metabolism
/ Biological and medical sciences
/ Breast Neoplasms - immunology
/ Breast Neoplasms - pathology
/ Calcium-Binding Proteins - genetics
/ Calcium-Binding Proteins - metabolism
/ Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
/ Female
/ Fundamental and applied biological sciences. Psychology
/ Gene Expression Regulation, Neoplastic
/ Gynecology. Andrology. Obstetrics
/ Humans
/ Interferon-gamma - metabolism
/ Medicine
/ Molecular and cellular biology
/ Oncology
/ Tumors
