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Molecular mechanisms of amoeboid invasion of cancer cells
Paňková, Daniela ; Brábek, Jan (advisor) ; Dvořák, Michal (referee) ; Vomastek, Tomáš (referee)
Tumour cell invasion is one of the most critical steps in malignant progression. It includes a broad spectrum of mechanisms, including both individual and collective cell migration, which enables them to spread towards adjacent tissue, and form new metastases. Understanding the mechanisms of cell spreading, and invasion, is crucial for effective anticancer therapy. Two modes of individual migration of tumour cells have been established in a three-dimensional environment. Mesenchymally migrating cells use proteases to cleave collagen bundles, and thus overcome the ECM barriers. Recently described protease-independent amoeboid mode of invasion has been discovered in studies of cancer cells with protease inhibitors. During my PhD study, I have focused on determining the molecular mechanisms involved in amoeboid invasion of tumour cells. We have examined invasive abilities in non-metastatic K2 and highly metastatic A3 rat sarcoma cell lines. We have shown that even though highly metastatic A3 rat sarcoma cells are of mesenchymal origin, they have upregulated Rho/ROCK signalling pathway. Moreover, A3 cells generate actomyosin-based mechanical forces at their leading edges to physically squeeze through the collagen fibrils by adopting an amoeboid phenotype. Amoeboid invasiveness is also less dependent on...
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Polydendrocytes and their role in CNS
Suchá, Petra ; Anděrová, Miroslava (advisor) ; Tvrdoňová, Vendula (referee)
Polydendrocytes (NG2+ cells) are recently discovered glial cells in central nervous system (CNS) distinct from neurons, oligodendrocytes, astrocytes and microglia. Polydendrocytes could be identified mainly by the expression of the proteoglycan NG2 and platelet derived growth factor receptor alpha. They could be found in grey and white matter and represent the largest proliferating cell population in adult CNS. It is accepted that a subpopulation of polydendrocytes gives rise to oligodendrocytes not only in development, but also in adult CNS and after demyelination. A subpopulation gives rise also to protoplasmic astrocytes in embryonic development. In in vitro studies was observed that neurons and astrocytes may arise from polydendrocytes. Electrophysiological studies revealed that polydendrocytes form synapses with neurons and that their rate of proliferation could be controlled this way. Polydendrocytes are very important in study of remyelination after ischemia and demyelinating diseases, as they might serve as source of new oligodendrocytes or possibly of another glial cells. This thesis summaries general knowledge about polydendrocytes. Initially, I focus on their immunohistochemical markers and morphology. Next, I summarise findings about their development and fate in both embryonic and adult CNS. A...
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Polydendrocytes and their role in CNS
Suchá, Petra ; Anděrová, Miroslava (advisor) ; Tvrdoňová, Vendula (referee)
Polydendrocytes (NG2+ cells) are recently discovered glial cells in central nervous system (CNS) distinct from neurons, oligodendrocytes, astrocytes and microglia. Polydendrocytes could be identified mainly by the expression of the proteoglycan NG2 and platelet derived growth factor receptor alpha. They could be found in grey and white matter and represent the largest proliferating cell population in adult CNS. It is accepted that a subpopulation of polydendrocytes gives rise to oligodendrocytes not only in development, but also in adult CNS and after demyelination. A subpopulation gives rise also to protoplasmic astrocytes in embryonic development. In in vitro studies was observed that neurons and astrocytes may arise from polydendrocytes. Electrophysiological studies revealed that polydendrocytes form synapses with neurons and that their rate of proliferation could be controlled this way. Polydendrocytes are very important in study of remyelination after ischemia and demyelinating diseases, as they might serve as source of new oligodendrocytes or possibly of another glial cells. This thesis summaries general knowledge about polydendrocytes. Initially, I focus on their immunohistochemical markers and morphology. Next, I summarise findings about their development and fate in both embryonic and adult CNS. A...
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Molecular mechanisms of amoeboid invasion of cancer cells
Paňková, Daniela ; Brábek, Jan (advisor) ; Dvořák, Michal (referee) ; Vomastek, Tomáš (referee)
Tumour cell invasion is one of the most critical steps in malignant progression. It includes a broad spectrum of mechanisms, including both individual and collective cell migration, which enables them to spread towards adjacent tissue, and form new metastases. Understanding the mechanisms of cell spreading, and invasion, is crucial for effective anticancer therapy. Two modes of individual migration of tumour cells have been established in a three-dimensional environment. Mesenchymally migrating cells use proteases to cleave collagen bundles, and thus overcome the ECM barriers. Recently described protease-independent amoeboid mode of invasion has been discovered in studies of cancer cells with protease inhibitors. During my PhD study, I have focused on determining the molecular mechanisms involved in amoeboid invasion of tumour cells. We have examined invasive abilities in non-metastatic K2 and highly metastatic A3 rat sarcoma cell lines. We have shown that even though highly metastatic A3 rat sarcoma cells are of mesenchymal origin, they have upregulated Rho/ROCK signalling pathway. Moreover, A3 cells generate actomyosin-based mechanical forces at their leading edges to physically squeeze through the collagen fibrils by adopting an amoeboid phenotype. Amoeboid invasiveness is also less dependent on...
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