Normal and Malignant Germ Cell Development
(Normale en maligne ontwikkeling van kiemcellen)
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All articles of this thesis are reproduced with kind permission. Permission is granted by Oxford Journals (chapter 2), John Wiley & Sons Ltd. on behalf of PathSoc. (chapters 3, 5 and 6), Elsevier (chapter 4, and Nature Publishing Group (chapter 7).
Defining normal and malignant germ cell development is crucial for understanding the biology and behaviour of germ cell tumours. Germ cell tumours show significant similarities with immature germ cells. Furthermore, treatment sensitivity of germ cell tumours reflects the intrinsic characteristics of the cell of origin. The aim of this thesis was to identify factors involved in the development of normal and malignant human germ cells. The marker profile of male and female germ cells during normal foetal development was established and compared to the profile found in dysgenetic gonads. Furthermore, the role of extracellular factors like the microenvironment was addressed, and links between pluripotency, cellular differentiation, and treatment response were investigated. A number of markers for early germ cells could be confirmed and further characterized. From our results, we conclude that external factors like cell-cell signalling create a niche that is essential to ensure normal germ cell development. The analyses were then extended to tissue samples showing delayed or disturbed maturation. An amazing finding was the detection of germ cell-lineage differentiation in nonseminomatous germ cell tumours. Human germ cell tumours must therefore be regarded as truly totipotent tumours with unrestricted developmental potential. Finally, our investigations present findings of different factors supposedly involved in chemotherapy resistance. Rather than being involved in treatment resistance, several factors investigated were found to be differentially regulated during germ cell development. This illustrates that in germ cell tumours it is particularly important to be able to interpret results in view of aspects of developmental biology.
Looijenga, Prof. Dr. L.H.J. (promotor)
Oosterhuis, Prof. Dr. J.W. (promotor)
- germ cells
- oct 3/4
- germ cell development
- germ cell tumors