Dataset Information

Proteomic Analysis of Canine Extracellular Matrix in Mammary Tumor Progression

ABSTRACT: Canine mammary gland tumors are common and bear striking similarities to human breast cancer, making them a valuable model for comparative oncology. This study examined changes in the extracellular matrix (ECM) associated with tumor progression in spontaneous canine mammary carcinomas, aiming to identify biomarkers linked to tumor aggressiveness. Normal, non-metastatic, and metastatic mammary tissues were analyzed by histological and proteomic approaches, and human breast cancer transcriptomic data were explored for in silico validation. Histological analysis with special stains revealed a reduction in type III collagen in metastatic tumors. The proteomic profile identified 12 MEC-related proteins with differential expressions in canine samples, of which eight were upregulated (COL12A1, COL4A1, COL4A2, SERPINH1, SERPINF1, HTRA1, TNC, PCOLCE) and four (MMRN1, ABI3BP, DPT, OGN) were downregulated and were confirmed to be differentially expressed in the human transcriptome as well. The results highlight the active remodeling of the ECM during tumor progression, marked by increased expression of proteins associated with stiffness and invasiveness and decreased expression of potential suppressors. These findings strengthen the understanding of ECM dynamics in breast cancer and suggest promising molecular targets for future investigations.

INSTRUMENT(S):

ORGANISM(S): Canis Familiaris (dog) (canis Lupus Familiaris)

TISSUE(S): Extracellular Matrix, Mammary Gland Tumor Cell, Mammary Gland

DISEASE(S): Breast Cancer

SUBMITTER: Michel Batista

LAB HEAD: Karine Araújo Damasceno

PROVIDER: PXD074203 | Pride | 2026-04-13

REPOSITORIES: Pride

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			Action	DRS
	20231110_201323_Dalila_1E_2.raw	Raw
	20231110_201323_Dalila_1E_3.raw	Raw
	20231110_201423_Dalila_2E_1.raw	Raw
	20231110_201423_Dalila_2E_2.raw	Raw
	20231110_201523_Dalila_3E_1_20231116081117.raw	Raw

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Publications

Comparative omics reveals conserved extracellular matrix signatures during mammary tumor progression.

de Almeida Bruno Sousa BS Rocha Gisele Vieira GV Nunes Simone S Zanette Dalila Luciola DL Batista Michel M Estrela-Lima Alessandra A Regis-Silva Carlos Gustavo CG Damasceno Karine Araújo KA

Frontiers in oncology 20260324

The extracellular matrix (ECM) plays a critical role in tumor progression by modulating cell adhesion, migration, and signaling; however, its contribution to metastatic progression in spontaneous mammary tumors remains poorly understood. Mammary tumors are among the most common neoplasms in female dogs and share histopathological and molecular similarities with human breast cancer, supporting their use as a comparative oncology model. To investigate ECM remodeling during tumor progression, we an ...[more]

PMID: 41952687

Similar Datasets

Project description:[original title] Metastatic Canine Mammary Carcinomas can be Identified by a Gene Expression Profile that partly Overlaps with Human Breast Cancer Profiles. Introduction: Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Methods: Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Results: Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Conclusions: Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a translational model for human breast tumors in order to identify prognostic molecular signatures and potential therapeutic targets. Thirteen simple mammary carcinomas with invasive growth and lymph node metastases at the time of tumor resection and 14 simple carcinomas without lymph node metastases were included in the study. None of the patients had radiographically detectable pulmonary metastases at the time of tumor resection. Distant metastases as the cause of death were determined postoperatively by radiographic detection of metastases or necropsy. Selection criteria for carcinomas without lymph node metastases included an invasive growth, a negative lymph node status, a histological grade III and a minimal tumor diameter above the average of the lymph node positive tumors (> 2.42 cm). All animals with non-metastatic carcinomas had a survival rate of over 24 months except animal no. 22 (2627) which developed radiographic detectable lung metastases 8 months after surgery. Tumor and lymph node histologies were evaluated independently by two board-certified pathologists, following the criteria of the WHO classification of canine mammary tumors and the Nottingham grading system. All 27 tumors were simple carcinomas and characterized by an invasive, mostly solid growth pattern, marked cellular pleomorphism, anisokaryosis and 3 or more mitotic figures per high power field.

Project description:Proliferation, dedifferentiation, loss of cell-cell contacts and angiogenesis are among the first steps of the metastasis cascade. The complex molecular pathways associated with these events in canine mammary tumors are mostly unknown and the value of this spontaneous canine tumor as a comparative model for human breast cancer is therefore still under debate. Messenger RNA profiles of lymph-node positive canine mammary carcinomas and normal mammary glands of the same dogs were compared by microarray analysis to elucidate molecular pathways associated with metastatic progression. Differential gene expression was analyzed by gene set enrichment and pathway analysis and compared with the gene expression data of human breast cancer. Metastatic canine carcinomas had 1,312 significantly differentially expressed genes when compared to the corresponding normal mammary gland. This expression profile included a significantly increased expression of cell division and extracellular matrix invasion genes (MMP1, MMP11, MMP13, SERPINE1, TFPI2, TIMP3). In contrast, genes associated with epithelial differentiation (EGF, EGFR, KRT17, MAP2K6, STAT5), cell adhesion (CLDN5, CLDN8, CTNNAL1, MCAM, MUC1, PECAM1) and angiogenesis (ANGPT2, ANGPTL1, ANGPTL2, ANGPTL4, FGFR1, FIGF, TIE1) were mostly down-regulated. Interestingly, tumors had a significant decrease in membrane receptors and growth factor pathway gene expression (EGFR, FGFR1, GHR, LYVE1, PDGFR, PDGFR, TGFBR, TIE1), indicating a potential independence from these proliferative stimuli. Several of the identified deregulated pathways overlap with gene expression profiles of human breast cancer. Gene expression profiling of metastatic carcinomas therefore identified complex molecular pathways and functional gene families that are deregulated during malignant progression in the tumors. This study provides new insights into canine mammary tumor metastasis and suggests that canine mammary tumors may serve as a valuable model for the human disease.