Tesis doctoral de Joanna Biela¿ska
The main aim of this project was to investigate the role of two members of voltage-gated potassium channel family, kv1.3 and kv1.5, in cell procceses such as proliferation, differentiation and activatian, and in cancer. the first part of the study was focused on activation and differentiation of immune system cells where kv1.3 and kv1.5 channels play a key role during the immune response. Our results demonstrate that the immunomodulatory changes of the stoichiometry of kv1.3 and kv1.5 in heterotetrameric complexes have important biophysical and pharmacological consequences for macrophage physiology. These changes, which are accounted for a specific regulation of kv.13, are common feature for professional antigen presenting cells. we have also studied more in depth the expression of voltage-gated potassium channels kv1.3 and kv1.5 in human cancer. This part of our investigation included a wide study of expression of kv1.3 and kv1.5 in a plethora of different types of cancer and two more focused studies on lymphoma and muscle tumours. the results show that kv1.3 and kv1.5 are differentially remodeled in many human cancers. Although there is not a general pattern, both channels could serve as novel markers of metastatic phenotype and as potential new therapeutic targets in specific tumors. we could also show kv1.3 and kv1.5 remodeled in human non-hodgkin lymphomas. While kv1.3 abundance is highly variable and probably reflects different levels of leukocyte activation, kv1.5 follows an inverse correlation with activation, dedifferentiation and malignancy. we have also found that skeletal and smooth muscle carcinogenesis triggers kv1.3 and kv1.5 remodeling depending on the cancer type and malignancy. While the impaired expression of kv1.5 would be more related to aggressive skeletal muscle sarcoma, kv1.3 points out to smooth muscle tumorigenesis. finally, we investigated the expression of kv1.3 and kv1.5 during human fetal development. Kv1.3 and kv1.5 were highly expressed in sensory, epithelia and endocrine tissues in human fetus. In addition, hematopoietic fetal liver expressed a notable amount of both proteins. Our results suggest that the ontogenetic regulation of these channels may play a crucial role for the development of the mature kv channel pattern in human. this work adds some interesting information to the field of kv channels and disease. We confirmed that kv1.3 and kv1.5 are involved in cellular processes such as activation and differentiation, which are very important for the proper functioning of the organism. In pathological conditions these channels are differentially remodeled, which makes them good candidates for therapeutic targets and diagnostic markers of metastatic phenotype in specific types of cancer.
Datos académicos de la tesis doctoral «Kv1.3 and kv1.5 in human cancer and their role in leukocyte phisiology«
- Título de la tesis: Kv1.3 and kv1.5 in human cancer and their role in leukocyte phisiology
- Autor: Joanna Biela¿ska
- Universidad: Barcelona
- Fecha de lectura de la tesis: 25/01/2011
Dirección y tribunal
- Director de la tesis
- Antonio Felipe Campo
- Tribunal
- Presidente del tribunal: josep Mª Argilés huguet
- Luis angel Pardo fernandez (vocal)
- (vocal)
- (vocal)