Katalin Dobra

Proteoglycan syndecan-1 (sdc1) is a molecule in the cell membrane, where it manages cell interactions with its environment. Syndecan-1 is important for mesothelioma cell maturation, and is linked to good prognosis, while if it is cut from the cell surface due to various enzymatic reactions, mesothelioma cells become more aggressive and the prognosis deteriorates. We have found that sdc-1 can also be transported to the cell nucleus, where it inhibits the cell's growth and ability to move, which are central functions of cancer cells. We have mapped the Sdc-1 structure in detail and was able to identify a minimal structure sufficient to reduce cell growth. We test sdc1 as a diagnostic biomarker when analyzing both blood samples and fluid from the pulmonary sacs. To achieve clinical utility, sdc1 must be measured together with other markers. In a first sub-project, we will find out how cells with different levels of sdc1 in the nucleus differ and which substances interact with sdc1 in the cell nucleus. A short sequence of the sdc1 molecule RMKKK that directs it into the nucleus is tested as possible growth inhibitor. We also test if sdc-1 can participate in uptake of different drugs and if it is important for communication between cells through vesicular structures, so-called exosomes. When we have learned to better understand how sdc1 links different signal paths, it gives a basic knowledge of how different cell functions are regulated. It will then give us valuable tools to attack tumor cells. Sdc1 affects a number of growth factors against which there are specific chemo. Sdc1 can therefore be a molecule that can specifically mediate the treatment of tumors. The biomarker analysis aims to be able to diagnose malignant mesothelioma at an earlier stage and provide increased possibilities for cure for patients.

The proteoglycan syndecan-1 (sdc1) is a molecule in the cell membrane, where it manages the cell's interaction with its environment. We have found that it can also go to the cell nucleus, where it regulates the cell's growth and ability to move, which are central functions of cancer cells. During the fetus, the body's supporting tissues and epithelium develop. Sometimes the cells switch between these main groups, ie they can switch from connective tissue to epithelium (MET) and vice versa (EMT), a process called trans-differentiation. In the tumor malignant mesothelioma, this transdifferentiation can be induced in experiments, making it possible to study the process more closely. We test sdc1 as a diagnostic biomarker when analyzing both blood samples and fluid from the pulmonary sacs. To achieve clinical utility, sdc1 must be measured together with other markers. In a first sub-project, we will find out how cells with different levels of sdc1 in the nucleus differ and which substances interact with sdc1 in the cell nucleus. We will also study how the varying level of sdc1 in the core of mesothelioma cells affects the division of the cell, growth, motility and neovascularization. A short sequence of the sdc1 molecule that directs it into the nucleus is tested as possible growth inhibitor. When we learned to better understand how sdc1 links different signal paths, it gives a basic knowledge of how different cell functions are regulated. It will then include factors that can be attacked in malignant tumors. Sdc1 affects a number of growth factors against which there are specific chemo. Sdc1 can therefore be a molecule that can specifically mediate the treatment of tumors. The biomarker analysis aims to be able to diagnose malignant mesothelioma at an earlier stage and provide increased opportunities for curative treatment.

The proteoglycan syndecan-1 (sdc1) is a molecule in the cell membrane, where it manages the cell's interaction with its environment. We have found that it can also go to the cell nucleus, where it regulates the cell's growth and ability to move, which are central functions of cancer cells. During the fetus, the body's supporting tissues and epithelium develop. Sometimes the cells switch between these main groups, ie they can switch from connective tissue to epithelium (MET) and vice versa (EMT), a process called trans-differentiation. In the tumor malignant mesothelioma, this transdifferentiation can be induced in experiments, making it possible to study the process more closely. We test sdc1 as a diagnostic biomarker when analyzing both blood samples and fluid from the pulmonary sacs. To achieve clinical utility, sdc1 must be measured together with other markers. In a first sub-project, we will find out how cells with different levels of sdc1 in the nucleus differ and which substances interact with sdc1 in the cell nucleus. We will also study how the varying level of sdc1 in the core of mesothelioma cells affects the division of the cell, growth, motility and neovascularization. A short sequence of the sdc1 molecule that directs it into the nucleus is tested as possible growth inhibitor. When we learned to better understand how sdc1 links different signal paths, it gives a basic knowledge of how different cell functions are regulated. It will then include factors that can be attacked in malignant tumors. Sdc1 affects a number of growth factors against which there are specific chemo. Sdc1 can therefore be a molecule that can specifically mediate the treatment of tumors. The biomarker analysis aims to be able to diagnose malignant mesothelioma at an earlier stage and provide increased opportunities for curative treatment.

The proteoglycan syndecan-1 (sdc1) is a molecule in the cell membrane, where it manages the cell's interaction with its environment. We have found that it can also go to the cell nucleus, where it regulates the cell's growth and ability to move, which are central functions of cancer cells. During the fetus, the body's supporting tissues and epithelium develop. Sometimes the cells switch between these main groups, ie they can switch from connective tissue to epithelium (MET) and vice versa (EMT), a process called trans-differentiation. In the tumor malignant mesothelioma, this transdifferentiation can be induced in experiments, making it possible to study the process more closely. We test sdc1 as a diagnostic biomarker when analyzing both blood samples and fluid from the pulmonary sacs. To achieve clinical utility, sdc1 must be measured together with other markers. In a first sub-project, we will find out how cells with different levels of sdc1 in the nucleus differ and which substances interact with sdc1 in the cell nucleus. We will also study how the varying level of sdc1 in the core of mesothelioma cells affects the division of the cell, growth, motility and neovascularization. A short sequence of the sdc1 molecule that directs it into the nucleus is tested as possible growth inhibitor. When we learned to better understand how sdc1 links different signal paths, it gives a basic knowledge of how different cell functions are regulated. It will then include factors that can be attacked in malignant tumors. Sdc1 affects a number of growth factors against which there are specific chemo. Sdc1 can therefore be a molecule that can specifically mediate the treatment of tumors. The biomarker analysis aims to be able to diagnose malignant mesothelioma at an earlier stage and provide increased opportunities for curative treatment.

This project aims to study syndecan-1 as a possible biomarker and create an understanding of the process called transdifferentiation, where the proteoglycan syndecan-1 (sdc1) is an important co-player. During the fetal period, the body develops from three main types of tissue. One of these gives rise to the body's supporting tissues. During this development, the constituent cells are transformed, sometimes so as to switch appearance and function between the main groups, ie transitions from connective tissue to epithelium (MET) and vice versa (EMT). In the adult individual, such transdifferentiation can take place, for example, in tumors, where EMT causes a more difficult-to-treat condition with poorer prognosis. Sdc1 is a molecule in the cell membrane that manages the cell's interactions with its environment. A few years ago we showed that sdc1 also goes to the nucleus of the cell, and our preliminary results indicate that the one that regulates the cell's growth and ability to move, ie central functions for cancer cells. In these systems we will study more precisely which of the sdc1's functions are of importance for the mesothelioma cell transdifferentiation, which also gives knowledge of what makes that tumor so difficult to treat. We have recently been able to show that a short sequence of the sdc1 molecule is what directs it into the nucleus and it slows the growth of mesothelioma cells. We will study how mesothelioma cells with varying levels of sdc1 in the nucleus grow, divide and move. Of central importance to this project is also to link this to the cell's growth mode. This is done partly by showing with different antibodies markers for the different forms of the transdifferentiation. When we learned to better understand how transdifferentiation works, we gain through this important knowledge of malignant tumors that are used directly for diagnostic and treatment purposes. In pleural fluid and blood samples, syndecan-1 can be used to enable early diagnosis and thereby improve the patient's possibilities for successful treatment.