Grønlund, Sara

Gugerel, Marietta

Olsson, Josephine

Pedersen, Kristian Jensen

Profft, Stefan

This project will describe the metastasis process, the metastasis promoting proteins S100A4 and uPA, analyze functional mouse model studies of S100A4 and uPA, and discuss the quality of these models. Metastasis causes 90 % of all deaths among cancer patients. Metastasis of the tumor is a process of several combined steps and comprised of; local invasion, intravasation, survival in the blood steam, arrest at a distant organ, extravasation, creation of micro metastasis and metastatic colonization. The S100A4 protein has been shown to play a major role in several cancer types ability to form metastases, because the protein has influence both intra- and extracellularly. S100A4 regulates cell motility, cell adhesion, apoptosis, cytoskeleton dynamics and angiogenesis. uPA also plays a part in metastasis by activating plasmin and thereby start the degradation of the ECM, and uPA also stimulates the metastasis process by upregulating growth factors such as VEGF. Both syngene, xenogene transplant mouse models, transgene models such as PyMT mouse models and knockout models are used to study the metastasis process and the function of metastasis inducing proteins. Results from the studies of S100A4 and uPA, points towards them both having a big influence in the development of metastasis, and that the stroma surrounding the tumor has a key role in understanding metastasis. The surrounding stroma is of interest because both S100A4 and uPA interact with it. For example, S100A4 has been shown to be essential for a non-metastatic cancer to form a metastatic phenotype. The projects purpose is to illuminate if the conditions of the mouse models are optimal, if the metastasis process in the mouse model can be used to understand human cancer better, and if yes to what degree. The advantages and disadvantages there is with the use of mouse models will be discussed. The aforementioned mouse models can be used to give an idea of what role proteins have in cancer and metastasis, but all such results must be viewed from a critical standpoint. There is still no ideal model to study the metastasis process, because none of the aforementioned mouse models represents the entire process or represents realistic circumstances. Cre-loxP technology have made mouse models better, by making it possible to control the expression of proteins in specific tissue. To describe processes like the metastasis process completely a better model is still needed with more advanced mice.This project will describe the metastasis process, the metastasis promoting proteins S100A4 and uPA, analyze functional mouse model studies of S100A4 and uPA, and discuss the quality of these models. Metastasis causes 90 % of all deaths among cancer patients. Metastasis of the tumor is a process of several combined steps and comprised of; local invasion, intravasation, survival in the blood steam, arrest at a distant organ, extravasation, creation of micro metastasis and metastatic colonization. The S100A4 protein has been shown to play a major role in several cancer types ability to form metastases, because the protein has influence both intra- and extracellularly. S100A4 regulates cell motility, cell adhesion, apoptosis, cytoskeleton dynamics and angiogenesis. uPA also plays a part in metastasis by activating plasmin and thereby start the degradation of the ECM, and uPA also stimulates the metastasis process by upregulating growth factors such as VEGF. Both syngene, xenogene transplant mouse models, transgene models such as PyMT mouse models and knockout models are used to study the metastasis process and the function of metastasis inducing proteins. Results from the studies of S100A4 and uPA, points towards them both having a big influence in the development of metastasis, and that the stroma surrounding the tumor has a key role in understanding metastasis. The surrounding stroma is of interest because both S100A4 and uPA interact with it. For example, S100A4 has been shown to be essential for a non-metastatic cancer to form a metastatic phenotype. The projects purpose is to illuminate if the conditions of the mouse models are optimal, if the metastasis process in the mouse model can be used to understand human cancer better, and if yes to what degree. The advantages and disadvantages there is with the use of mouse models will be discussed. The aforementioned mouse models can be used to give an idea of what role proteins have in cancer and metastasis, but all such results must be viewed from a critical standpoint. There is still no ideal model to study the metastasis process, because none of the aforementioned mouse models represents the entire process or represents realistic circumstances. Cre-loxP technology have made mouse models better, by making it possible to control the expression of proteins in specific tissue. To describe processes like the metastasis process completely a better model is still needed with more advanced mice

De metastase-fremmende proteiner S100A4 og uPAs rolle i metastaseprocessen med musemodeller

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Roskilde Universitet