Serological proteome analysis of dogs with breast cancer unveils common serum biomarkers with human counterparts

Abstract

Canine mammary tumor is being touted as a model for investigating the human breast cancer. Breast cancer of the both species has similar biological behavior, histopathologic characteristics, and metastatic pattern. In this study, we used the serological proteome analysis to detect autoantigens that elicit a humoral response in dogs with mammary tumor in order to identify serum biomarkers with potential usefulness as diagnostic markers and to better understand molecular mechanisms underlying canine breast cancer development. Protein extract from a cell line was subject to 2DE followed by Western blotting using sera from 15 dogs with mammary tumor and sera from 15 healthy control dogs. Immunoreactive autoantigens were subsequently identified by the MALDI-TOF MS. Four autoantigens, including manganese-superoxide dismutase, triose phosphate isomerase, alpha-enolase, and phosphoglycerate mutase1, with significantly higher immunoreactivity in the tumor samples than in the normal samples were identified as biomarker candidates. Immunohistochemistry and Western blotting revealed higher expression of these biomarkers in the malignant tumors than in the normal or benign tumors. The autoantigens found in this study have been reported to elicit autoantibody response in the human breast cancer, indicating the similarity of breast cancer proteome profile in dogs with that in human beings.

Antioxidant enzymes in canine mammary tumors

“…Brought to you by | MIT Libraries Authenticated Download Date | 5/9/18 1:31 PM MnSOD overexpression in canine mammary tumors reported in the present paper is in accordance with data presented by Zamani-Ahmadmahmudi et al [2]. The MnSOD overexpression in cancer cells compared to normal cells is a common fi nding in studies on different carcinomas [18], including also breast cancer [19].…”

“…The inactivation of the enzyme could be related also to the presence of autoantibodies against MnSOD. This hypothesis is supported by the identifi cation of serum autoantibodies against MnSOD in women [22] and bitches with mammary gland tumors [2].…”

“…In veterinary medicine, mammary tumors represent the most common malignant neoplasms in the bitch [1]; furthermore, they share a wide pathological and clinical heterogeneity with their human counterparts [2]. Investigations aimed at discovering clinical and pathologic parameters with prognostic and/or therapeutic signifi cance for these neoplasms are considered an important fi eld of study.…”

Immunohistochemical expression of manganese-superoxide dismutase (Mn-SOD) and triose-phosphate isomerase (TPI) in canine mammary gland tumor

“…We have recently identified potential serum biomarkers in dogs with breast cancer, which are similar to those in human patients (Zamani-Ahmadmahmudi et al 2014). Two enzymes, including manganese superoxide dismutase (Mn-SOD) and triose-phosphate isomerase (TPI), were found to elicit humoral immune response in canine mammary tumor, with the hope of using these enzymes as potential biomarkers for early diagnosis of breast cancer (Zamani-Ahmadmahmudi et al 2014).…”

“…Tamesa et al (2009) showed overexpression of TPI in 47 % of breast cancer patients. In addition, autoantibodies against TPI antigen were detected in both human and canine breast cancers (Tamesa et al 2009;Zamani-Ahmadmahmudi et al 2014).…”