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The role of galectins in cancer cell invasiveness
Remišová, Michaela ; Brábek, Jan (advisor) ; Kovář, Marek (referee)
Galectins are family of β-galactosidase binding proteins that serve many functions in all kind of mammalian cells. In the past years galectins, namely galectin-1 and galectin-3, have been revealed to play a major role in various cancer processes including cancer cell invasiveness, a process indispensable for the formation of metastasis. Both extracellular and intracellular forms of galectins modify the process of invasiveness in various ways, through interacting with different components of the cell or of the cell signalling pathways. The aim of this bachelor's thesis is to summarize mechanisms by which galectins promote cancer cell invasiveness. Keywords: galectins, galectin-1, galectin-3, invasiveness, cancer, metastasis
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Optimization of proces for detection of free tumor DNA in plasma and its clinical utility for colorectal cancer, lung cancer and pancreatic cancer patients
Belšánová, Barbora ; Benešová, Lucie (advisor) ; Tachezy, Ruth (referee)
In current days, examination of circulating tumor DNA (ctDNA) finds new use across different cancers. It is directed at tumor-derived short fragments of DNA present in peripheral blood of patiens (mainly in advanced stages). Due to its minimal invasivity, almost 100 % specificity and relatively high sensitivity in stage IV patients, this approch found its main potential clinical utility especially in early detection of disease relapse or progression after tumor resection (i.e. post-operative follow-up), prediction and monitoring of therapy response and estimation of prognosis. As a result of minute levels of ctDNA on a high background of other non-tumor DNA fragments present in plasma, a suitable method exhibiting highest sensitivity is the key for proper detection of this marker. The approach is predominantly based on initial identification of a mutation in tumor tissue and its subsequent detection in plasma. The present work is aimed at optimization of ctDNA isolation and method of its detection based on PCR amplification followed by heteroduplex analysis by denaturing capillary electrophoresis (DCE) to achieve highest sensitivity for detection of mutated fraction in plasma sample. I have applied the optimized protocol to examine ctDNA in three types of cancers, namely colorectal cancer (122...
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The localization and transport of extracellular matrix proteases
Lyková, Dominika ; Tolde, Ondřej (advisor) ; Doubravská, Lenka (referee)
Metastasis is the main cause of death from solid cancer. The dissemination of cancer cells from a primary tumour is a very complex process that involves many steps and cells must overcome many obstacles to colonize distant organs. The tumour microenvironment influences the mode and the dynamics of invasion of cancer cells. Cancer cells have the ability to adapt to distinct environmental conditions in order to stay motile. Invasive cancer cells form membrane protrusions called invadopodia that are able to degrade extracellular matrix. The formation of invadopodia by cancer cells is interconnected to the production of matrix metalloproteases (MMPs). Metastasizing tumour cells use MMPs to break through extracellular matrix barriers and migrate in dense matrix. Both invadopodia formation and MMPs secretion is crucial for the degradation of the extracellular matrix. The most important is the membrane bound MMP-14 (MT1-MMP) and soluble MMP-2 and MMP-9. The invasive structures of tumour cells and the proteolytic enzymes in 2D environment is well described. However, a suitable model of localization and transport of MMPs and connection with invadopodia of tumour cells in 3D environment is still lacking. This diploma thesis focused on the extension of current knowledge of these key MMPs and on the...
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Invasive structures of cancer cells in 3D environment
Lyková, Dominika ; Tolde, Ondřej (advisor) ; Libusová, Lenka (referee)
The ability of cells to migrate through tissue barriers plays an important role in physiological and pathological processes including immune response or invasiveness of cancer cells. The cells generate cytoplasmic protrusions called podosomes and invadopodia, collectively known as invadosomes or podosome-type adhesions (PTA), which are thought to be the key structures of cell invasion, especially of cancer cells during metastasis. Invadosomes are F-actin rich cell-matrix contacts with capability to degrade extracellular matrix components and are observed both in normal cells (such as monocytic cells, endothelial cells and smooth muscle cells) and in cancer cells. This bachelor thesis is focused on those in cancer cells, their initiation, regulation, function and morphology in 3D and in vivo and their requirement for tumor metastasis.
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Molecular mechanisms of fibroblastoid cell phenotype transitions:dedifferentiation of myofibroblasts and influencing of invasiveness and metastasis of sarcoma
Kosla, Jan
Fibroblasts are the principal cellular component of the connective tissue. They are a heterogeneous group of cells which contribute to the structure of connective tissue and wound healing by their ability to produce extracellular matrix (ECM). Fibroblasts and cells derived from them are involved in many pathological processes such as formation of malignant tumors and fibrosis. Tumor progression which finally leads to metastasis is a serious biomedical problem. There is a growing body of the recent evidence showing an important role of the tumor stroma and its interaction with cancer cells in cancer progression. Tumor stroma comprises mainly of myofibroblasts and their products, namely ECM, soluble factors, and enzymes. Myofibroblasts contribute more or less to all steps of cancer progression. Furthermore myofibroblasts play a key role in fibrosis, another serious human disease which is not efficiently treatable and which is associated with cancer progression. These facts made us to search for molecular means capable of eliminating the myofibroblastic phenotype. We succeeded to entirely dedifferentiate primary myofibroblasts by concomitant inhibition of TGFβ signaling and perturbation of MAPK signaling in a chick model that we have introduced. Malignant fibroblasts form sarcomas. ECM is the first...
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Regulation of transcription by proteins of the Early growth response and Myb families
Čermák, Vladimír ; Dvořák, Michal (advisor) ; Vomastek, Tomáš (referee) ; Elleder, Daniel (referee)
The regulation of transcription of tens of thousands of genes in a vertebrate organism is an enormously complex phenomenon which entails the participation of thousands of various regulatory proteins. The largest functional category of these regulators is accounted for by sequence-specific DNA-binding proteins known as transcription factors. Proteins of the EGR and Myb families of transcription factors are long-studied regulators of a variety of physiological processes including cellular proliferation and differentiation. The structural and physical aspects of their function have been well characterized. Their cell-type specific participation in complex gene-regulatory networks, on the other hand, is still incompletely understood and represents a major challenge in the respective research areas. Preliminary analysis of gene expression data from metastasizing PR9692 and non- metastasizing PR9692-E9 chicken sarcoma cell lines revealed that the transcription factor EGR1 is expressed at a higher level in metastasizing cells and can thus take part in the regulatory processes that underlie the differences between the two cell lines. Further investigation demonstrated that the introduction of exogenous EGR1 into PR9692-E9 cells restored their metastatic potential to a level indistinguishable from PR9692...
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Molecular mechanisms of fibroblastoid cell phenotype transitions:dedifferentiation of myofibroblasts and influencing of invasiveness and metastasis of sarcoma
Kosla, Jan ; Dvořák, Michal (advisor) ; Peková, Soňa (referee) ; Reiniš, Milan (referee)
Fibroblasts are the principal cellular component of the connective tissue. They are a heterogeneous group of cells which contribute to the structure of connective tissue and wound healing by their ability to produce extracellular matrix (ECM). Fibroblasts and cells derived from them are involved in many pathological processes such as formation of malignant tumors and fibrosis. Tumor progression which finally leads to metastasis is a serious biomedical problem. There is a growing body of the recent evidence showing an important role of the tumor stroma and its interaction with cancer cells in cancer progression. Tumor stroma comprises mainly of myofibroblasts and their products, namely ECM, soluble factors, and enzymes. Myofibroblasts contribute more or less to all steps of cancer progression. Furthermore myofibroblasts play a key role in fibrosis, another serious human disease which is not efficiently treatable and which is associated with cancer progression. These facts made us to search for molecular means capable of eliminating the myofibroblastic phenotype. We succeeded to entirely dedifferentiate primary myofibroblasts by concomitant inhibition of TGFβ signaling and perturbation of MAPK signaling in a chick model that we have introduced. Malignant fibroblasts form sarcomas. ECM is the first...
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Imunoterapie melanomu a pankreatického adenokarcinomu na myším modelu
JANDOVÁ, Linda
The aim of this thesis is focused on possibilities of cancer immunotherapy which was studied in mouse B16-F10 melanoma model and in mouse Panc02 pancreatic adenocarcinoma model. We compared the effect of various compounds stimulating both innate and adaptive immunity using in vivo and in vitro experiments. The study also monitors incidence of metastasis.
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The use of CAM assay for characterization and study of cancer cell invasive properties
Vágnerová, Lenka ; Dvořák, Michal (advisor) ; Geryk, Josef (referee)
The chorioallantoic membrane (CAM) of chicken embryos belongs to the in vivo model systems frequently used for the study of angiogenesis and cell invasiveness. Using CAM assay we have tested selected chicken sarcoma cell lines characterized by different angiogenic properties and different ability to form metastasis. In addition to CAM assay, several other methods have been used to characterize the phenotype of these cell lines. We have selected a few proteins which could significantly influence the angiogenic and metastatic properties of investigated cell lines. We have established cell lines stably overexpressing these genes and compared their phenotypes with parental cell lines. We have shown that genes encoding ISL1, ARNT2, PROM1, HOXA11 proteins participate, in our experimental model, in activation of programes controlling angiogenesis and cell invasion.
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Segmentation of 3D image data using advanced textural and shape features
Novosadová, Michaela ; PhD, Miloš Malínský, (referee) ; Jan, Jiří (advisor)
This thesis first describes theory of range of methods of textural and shape analysis. In several published articles some of the mentioned methods are used for automatic detection of lesion in spine in CT images. Some of these articles are shortly presented (in this thesis). Next part of the thesis includes description of various classifiers which are used for classification of feature vectors. Practical part of the thesis is a design and implementation of image data segmentation solution (metastatic lesions in vertebrae) with use of classification of feature vectors formed by texture and shape symptoms. The thesis also deals with the selection of significant features for segmentation. Segmentation algorithm is tested on medical data.
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