title: The potential role of COX-2 in cancer stem cell-mediated canine mammary tumor initiation: an immunohistochemical study.
abstract: 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.
authors.affiliation: Department of Veterinary Clinical Science, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. ; Department of Veterinary Science, College of Life Science and Technology, Southwest University for Nationalities, Chengdu 610041, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Veterinary Clinical Science, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Veterinary Clinical Science, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Xie
authors.affiliation: Department of Veterinary Clinical Science, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
authors.forename: Degui
authors.initials: D
authors.lastname: Lin
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D004283:Dog Diseases / Q000235:genetics* / Q000378:metabolism; D004285:Dogs; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry / Q000662:veterinary; D015674:Mammary Neoplasms, Animal / Q000235:genetics* / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D018960:Hyaluronan Receptors; D050814:Octamer Transcription Factor-3; D051546:Cyclooxygenase 2; D066246:ErbB Receptors
keywords: COX-2; cancer stem cells; canine mammary tumor; tumor initiation