Untersuchungen zur Expression ausgewählter Stammzellgene an embryonalen Geweben und Tumoren

Abstract

HMGA2 and miRNAs of C19MC and miR-371-3 are mainly expressed in embryonic tissues. Reexpression of these genes can be found in different types of tumours. The influence of the above mentioned genes on development and growth was investigated in placentas and testicular germ cell tumours, which mimic embryonic development. Invasive growth is a characteristic of placentas and tumours. Therefore, analysis of the underlying regulation processes in placental development might help to understand the induction of invasive behavior in tumours. In this thesis, investigation of spontaneous and induced abortions and of full-term placentas revealed increasing expression of miRNAs of C19MC with the progression of pregnancy. According to literature, this seems to be related to the regulation of invasive growth of trophoblast cells. Particularly the expression level of miRNAs of the miR-371-3 cluster showed strong interindividual differences. This was not caused by the site of the placenta where the sample has been taken from. Additionally, interindividual differences in expression of miR-371a-3p were also observed in serum samples. It remains to be elucidated whether or not they affect processes during prenatal life. Since there were no differences in expression of spontaneous compared to induced abortions, the miRNAs examined do not play an obvious role in miscarriage events. Investigations conducted in this thesis revealed high HMGA2 expression in first trimester placentas followed by a decline to a baseline level which can be observed until birth. High HMGA2 expression correlated with the low oxygen environment in the uterus in early pregnancy which is known to be a requirement for the proliferation of trophoblast cells. Hence, HMGA2 might function as a proliferation factor in this context. No difference in expression of spontaneous compared to induced abortions could be detected. This indicates that HMGA2 has no obvious role in spontaneous abortions. The stem cell factor HMGA2 was mainly detected in stromal cells of placental villi. This is in concordance with the previous finding that stem cell are located in the stroma of placental villi. Another interesting result of this thesis was the finding that in trophoblast cells HMGA2 is located mostly in the cytoplasma. Cytoplasmatic expression might be related to extravillous differentiation of cytotrophoblast as shown for HMGA1. While physiological expression of HMGA2 is mainly restricted to embryonic tissues and stem cells, reexpression can be observed in different types of tumours. Due to the fact that testicular germ cell tumours mimic embryonic tissues, HMGA2 expression was measured in different types of postpubertal testicular germ cell tumours. Tumours comprising of only one subgroup could be distinguished by qRT PCR expression levels. In frequently found mixed tumours, classification via HMGA2 expression is less distinct. By using HMGA2 immunohistochemistry subgroups could be distinguished. To establish HMGA2 in clinical application, the investigation should be extended on a larger sample. HMGA2 staining showed promising results in detecting choriocarcinoma components. Convincing evidence was found for HMGA2 as an appropriate marker for the detection of yolk sac components.