Immunological and pathobiological roles of fibulin-1 in breast cancer.
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.
Pupa
Serenella M
SM
Molecular Targeting Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milano, Italy.
Argraves
William S
WS
Forti
Stefania
S
Casalini
Patrizia
P
Berno
Valeria
V
Agresti
Roberto
R
Aiello
Piera
P
Invernizzi
Annamaria
A
Baldassari
Paola
P
Twal
Waleed O
WO
Mortarini
Roberta
R
Anichini
Andrea
A
Ménard
Sylvie
S
Argraves
Scott W
SW
D000911:Antibodies, Monoclonal / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D001943:Breast Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D002402:Cathepsin D / Q000378:metabolism; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D002135:Calcium-Binding Proteins; C060820:fibulin; D015847:Interleukin-4; D007371:Interferon-gamma; D002402:Cathepsin D