Changes in Serum and Salivary Proteins in Canine Mammary Tumors

The aim of this study was to evaluate changes in serum and saliva proteomes in canine mammary tumors (CMT) using a high-throughput quantitative proteomic analysis in order to potentially discover possible biomarkers of this disease. Proteomes of paired serum and saliva samples from healthy controls (HC group, n = 5) and bitches with CMT (CMT group, n = 5) were analysed using a Tandem Mass Tags-based approach. Twenty-five dogs were used to validate serum albumin as a candidate biomarker in an independent sample set. The proteomic analysis quantified 379 and 730 proteins in serum and saliva, respectively. Of those, 35 proteins in serum and 49 in saliva were differentially represented. The verification of albumin in serum was in concordance with the proteomic data, showing lower levels in CMT when compared to the HC group. Some of the modulated proteins found in the present study such as haptoglobin or S100A4 have been related to CMT or human breast cancer previously, while others such as kallikrein-1 and immunoglobulin gamma-heavy chains A and D are described here for the first time. Our results indicate that saliva and serum proteomes can reflect physiopathological changes that occur in CMT in dogs and can be a potential source of biomarkers of the disease.

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The Serum and Saliva Proteome of Dogs with Diabetes Mellitus

Animals ◽

10.3390/ani10122261 ◽

2020 ◽

Vol 10 (12) ◽

pp. 2261

Author(s):

Lorena Franco-Martínez ◽

Andrea Gelemanović ◽

Anita Horvatić ◽

María Dolores Contreras-Aguilar ◽

Vladimir Mrljak ◽

...

Keyword(s):

Diabetes Mellitus ◽

Diabetes Mellitus Type 1 ◽

Healthy Controls ◽

Serum Samples ◽

Proteomic Data ◽

Proteomic Approach ◽

Paired Serum ◽

Canine Diabetes Mellitus ◽

Type 1 Dm ◽

First Time

This study aims to evaluate the changes in salivary and serum proteomes that occur in canine diabetes mellitus type-1 (DM) through a high-throughput quantitative proteomic analysis. The proteomes of 10 paired serum and saliva samples from healthy controls (HC group, n = 5) and dogs with untreated DM (DM group, n = 5) were analyzed using Tandem Mass Tags (TMT)-based proteomic approach. Additionally, 24 serum samples from healthy controls and untreated DM were used to validate haptoglobin in serum. The TMT analysis quantified 767 and 389 proteins in saliva and serum, respectively. Of those, 16 unique proteins in serum and 26 in saliva were differently represented between DM and HC groups. The verification of haptoglobin in serum was in concordance with the proteomic data. Our results pointed out changes in both saliva and serum proteomes that reflect different physiopathological changes in dogs with DM. Although some of the proteins identified here, such as malate dehydrogenase or glyceraldehyde-3-phosphate dehydrogenase, were previously related with DM in dogs, most of the proteins modulated in serum and saliva are described in canine DM for the first time and could be a source of potential biomarkers of the disease. Additionally, the molecular function, biological process, pathways and protein class of the differential proteins were revealed, which could improve the understanding of the disease’s pathological mechanisms.

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Cyclooxygenase-2 Expression in Canine Mammary Tumors

Veterinary Pathology ◽

10.1354/vp.40-2-207 ◽

2003 ◽

Vol 40 (2) ◽

pp. 207-212 ◽

Cited By ~ 59

Author(s):

M. Doré ◽

I. Lanthier ◽

J. Sirois

Keyword(s):

Potential Role ◽

Mammary Tumorigenesis ◽

Mammary Tumors ◽

Cyclooxygenase 2 ◽

Benign Tumors ◽

Normal Mammary Gland ◽

Normal Gland ◽

Canine Mammary Tumors ◽

Cox 2 ◽

First Time

Mammary tumors are the most common neoplasms in female dogs. Induction of cyclooxygenase-2 (COX-2) has been implicated in various cancers in humans. However, expression of COX-2 has not been investigated in canine mammary tumors. Normal mammary gland ( n = 4), simple or complex adenomas ( n = 63), and simple or complex adenocarcinomas ( n = 84) were studied by immunohistochemistry. Results showed that COX-2 was not expressed in the normal gland but was detected in 24% of adenomas and in 56% of adenocarcinomas ( P < 0.001). The incidence of COX-2 expression and the intensity of the COX-2 signal were higher in adenocarcinomas than in adenomas ( P < 0.001). These results demonstrate for the first time that COX-2 is induced in a proportion of canine mammary tumors and that COX-2 expression is more frequent and more intense in malignant than in benign tumors, suggesting a potential role for COX-2 in canine mammary tumorigenesis.

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Naturally-Occurring Canine Mammary Tumors as a Translational Model for Human Breast Cancer

Frontiers in Oncology ◽

10.3389/fonc.2020.00617 ◽

2020 ◽

Vol 10 ◽

Cited By ~ 8

Author(s):

Mark Gray ◽

James Meehan ◽

Carlos Martínez-Pérez ◽

Charlene Kay ◽

Arran K. Turnbull ◽

...

Keyword(s):

Breast Cancer ◽

Human Breast Cancer ◽

Mammary Tumors ◽

Human Breast ◽

Translational Model ◽

Naturally Occurring ◽

Canine Mammary Tumors

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ANK2 Hypermethylation in Canine Mammary Tumors and Human Breast Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms21228697 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8697

Author(s):

Johannes J. Schabort ◽

A-Reum Nam ◽

Kang-Hoon Lee ◽

Seok Won Kim ◽

Jeong Eon Lee ◽

...

Keyword(s):

Mammary Tumors ◽

Comparative Approach ◽

Aberrant Methylation ◽

Human Breast ◽

Liquid Biopsies ◽

Comparative Oncology ◽

Specific Pcr ◽

Canine Mammary Tumors ◽

Tumor Types ◽

Tissue Biomarkers

Canine mammary tumors (CMT) constitute the most common tumor types found in female dogs. Understanding this cancer through extensive research is important not only for clinical veterinary applications, but also in the scope of comparative oncology. The use of DNA methylation as a biomarker has been noted for numerous cancers in the form of both tissue and liquid biopsies, yet the study of methylation in CMT has been limited. By analyzing our canine methyl-binding domain sequencing (MBD-seq) data, we identified intron regions of canine ANK2 and EPAS1 as differentially methylated regions (DMGs) in CMT. Subsequently, we established quantitative methylation specific PCR (qMSP) of ANK2 and EPAS1 to validate the target hypermethylation in CMT tissue, as well as cell free DNA (cfDNA) from CMT plasma. Both ANK2 and EPAS1 were hypermethylated in CMT and highlighted as potential tissue biomarkers in CMT. ANK2 additionally showed significant hypermethylation in the plasma cfDNA of CMT, indicating that it could be a potential liquid biopsy biomarker as well. A similar trend towards hypermethylation was indicated in HBC at a specific CpG of the ANK2 target on the orthologous human region, which validates the comparative approach using aberrant methylation in CMT.

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PKM2 in Canine Mammary Tumors: Parallels to Human Breast Cancer

Comparative Medicine ◽

10.30802/aalas-cm-20-000013 ◽

2020 ◽

Vol 70 (4) ◽

pp. 349-354

Author(s):

Hyo-Ju Lee ◽

Hyo-Jeong Han ◽

Ji-Young Lee ◽

Woo-Chan Son

Keyword(s):

Breast Cancer ◽

Human Breast Cancer ◽

Aerobic Glycolysis ◽

Prognostic Significance ◽

Tumor Grade ◽

Mammary Tumors ◽

Neoplastic Disease ◽

Human Breast ◽

Rate Limiting Step ◽

Canine Mammary Tumors

PKM2 is a pyruvate kinase isoform that is the final and rate-limiting step in aerobic glycolysis in tumor cells. Increased expression of PKM2 has been detected in human cancers. The present study examined the expression of PKM2 in canine mammary tumors and assessed its prognostic significance. Paraffin sections of 5 adenomas, 67 carcinomas, and 5 samples of nonneoplastic hyperplasia from 77 dogs, aged 8 to 18 y, were evaluated. Significantly higher levels of PKM2 were detected among the carcinomas compared with all other tissues examined. The level of PKM2 expression in carcinoma tissue correlated positively with the tumor grade. These findings suggest that PKM2 may have a similar role in canine mammary tumors to its role in human breast cancer. As such, canine mammary tumors may be useful models for studies focused on the progression of human neoplastic disease.

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A Role for T-Lymphocytes in Human Breast Cancer and in Canine Mammary Tumors

BioMed Research International ◽

10.1155/2014/130894 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 33

Author(s):

Maria Isabel Carvalho ◽

Isabel Pires ◽

Justina Prada ◽

Felisbina L. Queiroga

Keyword(s):

Breast Cancer ◽

T Lymphocytes ◽

Human Breast Cancer ◽

Survival Rates ◽

Mammary Tumors ◽

Treg Cells ◽

Th2 Cells ◽

Human Breast ◽

Canine Mammary Tumors ◽

As Relationship

Chronic inflammation in the tumor microenvironment has a prominent role in carcinogenesis and benefits the proliferation and survival of malignant cells, promoting angiogenesis and metastasis. Mammary tumors are frequently infiltrated by a heterogeneous population of immune cells where T-lymphocytes have a great importance. Interestingly, similar inflammatory cell infiltrates, cytokine and chemokine expression in humans and canine mammary tumors were recently described. However, in both species, despite all the scientific evidences that appoint for a significant role of T-lymphocytes, a definitive conclusion concerning the effectiveness of T-cell dependent immune mechanisms has not been achieved yet. In the present review, we describe similarities between human breast cancer and canine mammary tumors regarding tumor T-lymphocyte infiltration, such as relationship of TILs and mammary tumors malignancy, association of ratio CD4+/ CD8+ T-cells with low survival rates, promotion of tumor progression by Th2 cells actions, and association of great amounts of Treg cells with poor prognostic factors. This apparent parallelism together with the fact that dogs develop spontaneous tumors in the context of a natural immune system highlight the dog as a possible useful biological model for studies in human breast cancer immunology.

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Immunohistochemical Analysis of Na+/K+-ATPase and Bone Morphogenetic Protein-2 Expressions in Both Parenchymal and Stromal Cells from Benign and Malignant Canine Mammary Tumors

10.21203/rs.3.rs-431238/v1 ◽

2021 ◽

Author(s):

ozlem ozmen

Keyword(s):

Stromal Cells ◽

Malignant Tumors ◽

Breast Tumors ◽

Mammary Tumors ◽

Bone Morphogenetic Protein 2 ◽

Mammary Tissue ◽

Benign Tumors ◽

Ion Pump ◽

Human Breast ◽

Canine Mammary Tumors

Abstract Canine mammary tumors are the most common type of dog tumor, and they are similar to human breast tumors. Na+/K+-ATPase is a common plasma membrane ion pump with important physiological and pathophysiological functions. In mammary tumors, the tumor microenvironment was composed of a heterogeneous population of tumor cells and nearby endogenous stromal cells. Bone morphogenetic proteins (BMPs) regulate fetal development, tissue homeostasis and differentiation, and a variety of cellular functions. The purpose of this study is to examine the immunohistochemical expression of Na+/K+-ATPase and BMP-2 in tumoral and stromal cells from benign and malignant canine mammary tumors. In this study, ten benign and ten malignant mammary tumors from the archives of the Department of Pathology were used, with five normal breast tissues serving as controls. The results of the revealed that tumors had higher levels of Na+/K+-ATPase and BMP-2 expressions than normal mammary tissue. While both markers were expressed negatively or mildly in benign tumors, they increased significantly in malignant tumors. Both Na+/K+-ATPase and BMP-2 are expressed by tumoral and stromal cells in canine mammary tumors. When compared to compared to BMP-2, Na+/K+-ATPase expression was found to be more severe. This study found that Na+/K+-ATPase and BMP-2 can be used as markers of malignancy in canine mammary tumors and that stromal cells also play an important role in tumor progression. These findings also indicated that Na+/K+-ATPase and BMP-2 may be used for early diagnosis or as a potential target for treatment of canine and human breast tumors in the future.

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Proteomic Analysis Reveals Grb2 as a Key Regulator of Periodic Mechanical Stress Transduction in Chondrocytes

Cellular Physiology and Biochemistry ◽

10.1159/000485646 ◽

2017 ◽

Vol 44 (4) ◽

pp. 1509-1525 ◽

Cited By ~ 2

Author(s):

Shun Xu ◽

Zeng Li ◽

Zhen Wang ◽

Chenjun Zhai ◽

Wenwei Liang ◽

...

Keyword(s):

Mechanical Stress ◽

Proteomic Analysis ◽

Lentiviral Vector ◽

Biological Effects ◽

Growth Factor Receptor ◽

Fold Increase ◽

Mechanical Stimuli ◽

Proteomic Data ◽

Extracellular Signal ◽

First Time

Background/Aims: Periodic mechanical stress could significantly promote chondrocyte proliferation and matrix synthesis. However, the mechanisms underlying the ability of chondrocyte detecting and responding to periodic mechanical stimuli have not been well delineated. Methods: Quantitative proteomic analysis was performed to construct the differently expressed proteome profiles of chondrocyte under pressure. Then a combination of Western blot, quantitative real-time PCR, lentiviral vector and histological methods were used to confirm the proteomic results and investigate the mechanoseing mechanism. Results: Growth factor receptor-bound protein 2 (Grb2), a component of integrin adhesome, was found a 1.49-fold increase in dynamic stress group. This process was mediated through integrin β1, leading to increased phosphorylation of focal adhesion kinase (FAK) and extracellular signal–regulated kinase 1/2 (ERK1/2) respectively and then produce the corresponding biological effects. Conclusion: This was the first time to demonstrate Grb2 has such an important role in periodic mechanotransduction, and the proteomic data could facilitate the further investigation of chondrocytes mechanosensing.

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