Humoral Immune Response against Tumoral Mucin 1 (MUC1) in Breast Cancer Patients

2013 ◽  
Vol 28 (3) ◽  
pp. 318-325 ◽  
Author(s):  
Marina T. Isla Larrain ◽  
Andrea G. Colussi ◽  
Sandra O. Demichelis ◽  
Alberto Barbera ◽  
Aldo Cretón ◽  
...  

The aim of this study was to elucidate whether the IgG humoral immune response to breast cancer cells is directed to the aberrant mucin-1 (MUC1) associated to this type of cancer. To this aim, an adaptation of immunohistochemistry (IHC) was performed on samples of 45 breast cancer tissues, 12 benign disease tissues, and 31 normal tissues, incubated with matched serum samples from the same patients. Each serum sample was also incubated, with a modified immunocytochemistry (ICC), with MCF7 cells. In both techniques, serum was employed instead of the primary antibody. In the case of IHC, the reactivity with sera diminished when added after previous incubation of the tumor/tissue with an anti-MUC1 mAb; the reduction in reactivity was: from 93% to 44% in breast cancer tissues, and from 100% to 67% in benign disease tissues. The reactivity of normal samples (36%) remained unchanged. In the case of ICC, the reactivity with sera decreased after incubation with anti-MUC1 mAb from 71% to 16% in breast cancer tissues, from 83% to 0% in benign disease tissues, and from 52% to 10% in normal serum samples. These results were confirmed employing siRNA MUC1 transient gene knockdown. By Western blot analysis – after immunoprecipitation (IP) of the circulating MUC1– and ELISA, the TF antigen was detected in circulating MUC1 in all breast cancer and benign samples while Tn was detected in 38% of the samples. The existence of IgG autoantibodies against aberrantly glycosylated MUC1 may have a protective role and may contribute to a better prognosis in some patients. Enhancement of this natural immune response may constitute an alternative therapeutic strategy.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5237-5237
Author(s):  
Aurelia Rughetti ◽  
Angelo Fama ◽  
Silvia von Mensdorff-Pouilly ◽  
Federica Taurino ◽  
Hassan Rahimi ◽  
...  

Abstract MUC1 is a glycoprotein expressed on the luminal surface of simple epithelia. In carcinoma, MUC1 overexpression is associated with malignancy. In breast cancer patients, increased levels of circulating MUC1 (CA 15.3 tumor marker) are associated with poor prognosis (Tumour Biol.2005; 26:217–20). In myeloma, MUC1 overexpression correlates with apoptosis resistance. We have previously shown (Br J Haematol.2003; 120:344–52) that MUC1 is selectively found in differentiating erythroid cells suggesting a possible role as cross-talk molecule between erythroblasts and bone marrow microenvironment during erythropoiesis. In CD34+ cells cultured in the presence of EPO and SCF, MUC1 is expressed before Glycophorin A (GlyA) during the erythroid differentiation process, and disappears following GlyA up-regulation. Aiming to evaluate the role of MUC1 in the erythroid counterpart present in neoplastic haemopoiesis, we studied MUC1 serum circulating levels in patients affected by Ph-negative Myeloproliferative Chronic Disorders (MPD). We analysed serum samples from 42 MPD patients affected by Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) (N 25, 14, and 3, respectively). CA15.3 (soluble MUC1) levels were determined using the commercially available ADVIA Centaur CA 15.3 assay (Bayer Corporation, NY) and cut off level was set at 25 U/mL. As control group serum samples from healthy donors, matched for sex and age, were also analyzed. Evaluation of the humoral immune response to MUC1 protein core was performed in ELISA. Results indicated that CA15.3 levels were statistically higher in MPD patients than in the control group (p<0.005), this difference was more evident in PV patients (p<0.001) and in female cases (p<0.001). The JAK2V617F mutation status was not associated with CA15.3 values; similarly, neither the clinical or hematological features nor the clinical complications (thrombosis) were influenced byCA15.3 levels. Analysis of the humoral immune response to MUC1 core protein showed no substantial changes in serum anti-MUC1 IgG titers in PV patients, suggesting that in PV increase of soluble MUC1 does not induce immune responses against this self-antigen. Further studies are ongoing to investigate the significance of MUC1 in the development and onset of myeloproliferative disorders. In conclusion, MUC1 levels seem to be increased in PV patients, suggesting that further evaluations on large series of cases should include this test in the diagnostic work-up to PV patients.


2006 ◽  
Vol 30 (3) ◽  
pp. 248-256 ◽  
Author(s):  
Emiliano Pavoni ◽  
Andrea Pucci ◽  
Paola Vaccaro ◽  
Giorgia Monteriù ◽  
Adolfo De Pasquale Ceratti ◽  
...  

2008 ◽  
Vol 393 (2) ◽  
pp. 95-102 ◽  
Author(s):  
Bechr Hamrita ◽  
Karim Chahed ◽  
Maria Kabbage ◽  
Christelle Lemaitre Guillier ◽  
Mounir Trimeche ◽  
...  

Vaccine ◽  
2017 ◽  
Vol 35 (9) ◽  
pp. 1299-1305 ◽  
Author(s):  
M.L. Wumkes ◽  
A.M.T. van der Velden ◽  
E. de Bruin ◽  
A. Meerveld-Eggink ◽  
M.P.G. Koopmans ◽  
...  

2016 ◽  
Vol 66 (6) ◽  
pp. 645 ◽  
Author(s):  
Anshul Varshney ◽  
Nidhi Puranik ◽  
M. Kumar ◽  
A.K. Goel

Anthrax, caused by Bacillus anthracis is known to occur globally since antiquity. Besides being an important biothreat agent, it is an important public health importance pathogen also in countries like India. B. anthracis secretes three distinct toxins, namely protective antigen (PA), lethal factor (LF) and edema factor (EF). PA is the central moiety of the anthrax toxin complex and therefore has been a molecule of choice for vaccine development. PA has four different domains with different functions. In this study, the major domains of PA were cloned and expressed in bacterial system. The purified recombinant proteins were used to determine the humoral immune response by ELISA using 43 human cutaneous anthrax serum samples. The maximum immunoreactivity was observed with the whole PA protein followed by domain 2, 4 and 1. The study corroborated that in addition to full PA, individual domain 2 and 4 can also be good target for vaccine development as well as for serodiagnostic assays for cutaneous anthrax


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