J Vet Sci.  2015 Jun;16(2):225-231. 10.4142/jvs.2015.16.2.225.

The potential role of COX-2 in cancer stem cell-mediated canine mammary tumor initiation: an immunohistochemical study

  • 1Department of Veterinary Clinical Science, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. csama@sina.com
  • 2Department of Veterinary Science, College of Life Science and Technology, Southwest University for Nationalities, Chengdu 610041, China.


Increasing evidence suggests that cancer stem cells (CSCs) are responsible for tumor initiation and maintenance. Additionally, it is becoming apparent that cyclooxygenase (COX) signaling is associated with canine mammary tumor development. The goals of the present study were to investigate COX-2 expression patterns and their effect on CSC-mediated tumor initiation in primary canine mammary tissues and tumorsphere models using immunohistochemistry. Patterns of COX-2, CD44, octamer-binding transcription factor (Oct)-3/4, and epidermal growth factor receptor (EGFR) expression were examined in malignant mammary tumor (MMT) samples and analyzed in terms of clinicopathological characteristics. COX-2 and Oct-3/4 expression was higher in MMTs compared to other histological samples with heterogeneous patterns. In MMTs, COX-2 expression correlated with tumor malignancy features. Significant associations between COX-2, CD44, and EGFR were observed in low-differentiated MMTs. Comparative analysis showed that the levels of COX-2, CD44, and Oct-3/4 expression varied significantly among TSs of three histological grades. Enhanced COX-2 staining was consistently observed in TSs. Similar levels of staining intensity were found for CD44 and Oct-3/4, but EGFR expression was weak. Our findings indicate the potential role of COX-2 in CSC-mediated tumor initiation, and suggest that COX-2 inhibition may help treat canine mammary tumors by targeting CSCs.


cancer stem cells; canine mammary tumor; COX-2; tumor initiation

MeSH Terms

Antigens, CD44/genetics/metabolism
Biomarkers, Tumor/genetics/metabolism
Cell Transformation, Neoplastic/*genetics/metabolism
Cyclooxygenase 2/*genetics/metabolism
Dog Diseases/*genetics/metabolism
Mammary Neoplasms, Animal/*genetics/metabolism
Mammary Neoplasms, Experimental/*genetics/metabolism
Neoplastic Stem Cells/*metabolism
Octamer Transcription Factor-3/genetics/metabolism
Receptor, Epidermal Growth Factor/genetics/metabolism
Retrospective Studies
Antigens, CD44
Biomarkers, Tumor
Cyclooxygenase 2
Octamer Transcription Factor-3
Receptor, Epidermal Growth Factor
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