The aim of this thesis was to investigate additional molecular mechanisms besides the proto-oncogene c-KIT that may contribute to MCT development and carcinogenesis in dogs. In that context the so-called tumor microevolution seems to be important, for instance the acquirement of molecules that are normally restricted to other cell types but display advantages for tumor survival and tumor growth. The IL-2R and particularly the α-subunit CD25 seemed to be a promising target since the receptor promotes cell activation and proliferation in immune cells and expression of CD25 was correlated with a neoplastic mast cell phenotype in humans. Therefore two hypotheses were tested here, namely that the IL- 2R α-subunit CD25 is expressed by canine cutaneous MCT and differentiates neoplastic from non-neoplastic mast cells and that the remaining subunits and the ligand IL-2 are expressed as well and an increased IL-2R expression in higher grade tumors contributes to mast cell tumor proliferation.
The findings of the study supported the first hypothesis since CD25 was expressed by canine cutaneous MCT and was able to differentiate neoplastic from non-neoplastic resting mast cells but was also slightly expressed in non-neoplastic activated mast cells. The latter, however, unfortunately diminishes the applicability of CD25 as a reliable tumor marker for neoplastic mast cells in dogs. The second hypothesis was partially confirmed since the majority of canine cutaneous MCT expressed both the IL-2R and the ligand IL-2 but the protein expression was consistently decreased with increasing tumor grade. Thus IL-2R expression in canine MCT seems not to significantly contribute to MCT proliferation, at least not in malignant tumors.
Taken together this implies that the IL-2R may be more relevant for early MCT development and lower grade tumors but less important at later stages of malignancy. This should also be taken into consideration when dealing with new treatment options such as intratumoral IL-2 application because well differentiated tumors with high IL-2R expression may not be appropriate for this form of therapy.
Interleukin-2 Receptor Expression in Canine
Cutaneous Mast Cell Tumors
Publication date: 30/11/-0001
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