title: All subunits of the interleukin-2 receptor are expressed by canine cutaneous mast cell tumours.
abstract: Cutaneous mast cell tumours (MCTs) are among the most important skin tumours in dogs. Apart from c-KIT mutations, which are present in <18% of MCTs, little is known of the mechanisms of MCT development and independent growth of tumour cells. Recently, the α-subunit (CD25) of the interleukin (IL)-2 receptor (IL-2R) has been found to be expressed by canine cutaneous MCTs and this expression is negatively correlated with tumour grade. We thus hypothesized that the other two subunits of the IL-2R and the ligand IL-2 are also expressed and that IL-2-dependent pathways may have an impact on MCT development and independent tumour cell growth. Messenger RNA and protein expression levels of the IL-2R β-subunit (CD122), the IL-2R γ-subunit (CD132) and IL-2 were analyzed in canine cutaneous MCTs and compared with tumour grade and c-KIT mutation status. Eighty-six percent of the tumours expressed both subunits of the IL-2R and 64% expressed IL-2. In addition, neoplastic mast cells seem able to bind IL-2. IL-2Rγ and IL-2 protein expression levels were significantly decreased in higher grade tumours and IL-2 expression was significantly decreased in c-KIT mutated tumours. Thus, expression of the complete IL-2R and its ligand by canine cutaneous MCTs indicates a potential impact of IL-2R signalling in MCT development and tumour cell proliferation. The decrease in IL-2R expression with increasing histological evidence of malignancy suggests that the IL-2R may be more relevant for early MCT development and well-differentiated tumours.
authors.affiliation: Department of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Straße 15, 14163 Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Meyer
authors.forename: A D
authors.initials: AD
authors.lastname: Gruber
authors.forename: R
authors.initials: R
authors.lastname: Klopfleisch
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000378:metabolism; D034701:Mastocytosis, Cutaneous / Q000235:genetics / Q000378:metabolism / Q000662:veterinary*; D060787:Neoplasm Grading; D021122:Protein Subunits / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000662:veterinary*
chemical_list: D014408:Biomarkers, Tumor; D007376:Interleukin-2; D021122:Protein Subunits; D015375:Receptors, Interleukin-2; D019009:Proto-Oncogene Proteins c-kit