Thesis defence in the University of Oulu

Doctoral Candidate

Master of Science Minna Kihlström

Faculty and research unit

University of Oulu Graduate School, Faculty of Biochemistry and Molecular Medicine, Cell and cell-extracellular matrix research unit

Field of study

Biochemistry and molecular medicine

Date and time of the thesis defence

1.11.2019 12:00

Place of the thesis defence

Auditorium F202, Aapistie 5B, Faculty of Medicine, University of Oulu

Topic of the dissertation

Characterization of angiopoietin ligands: Role of angiopoietin-4 in retinal venous development and angiopoietin-2 variant in tumor vasculature

Opponent

Professor Marcus Fruttiger, Institute of Ophthalmology, University College London

Custos

Professor Lauri Eklund, Faculty of Biochemistry and Molecular Medicine, University of Oulu

Characterization of angiopoietin ligands in retinal and tumor vasculature

Angiogenesis, the formation of new blood vessels and their differentiation into the hierarchical network of capillaries, veins and arteries is necessary for embryonic development and growth. In adults, angiogenesis is required for, e.g., tissue repair but is also involved in the development of neovascular retinopathies and may accelerate tumor growth and metastasis.

Angiopoietin growth factors regulate the activity of the endothelial Tie2 tyrosine kinase receptor that is known to affect the vasculature both in development and disease. In this thesis, two poorly characterized angiopoietin growth factors, angiopoietin-4 (Angpt4) and angiopoetin-2 (Angpt2) isoform Angpt2443, were investigated.

In the first part of this thesis, Angpt4 was shown to be needed for venous maturation in the mouse retina. Functional studies showed that Angpt4 deficiency in mice results in slow venous flow, neural cell swelling and vision impairment. Biochemical and cell biological studies revealed how the effects of Angpt4 differ from the other angiopoietin family members. A novel growth factor regulating venous development and maturation was found in these studies that may lead to new treatment strategies for venous diseases.

In the second part of this thesis, the presence of Angpt2443 in mouse breast cancer disrupted blood vessel architecture, and reduced tumor growth and metastasis to the lungs. Protein studies revealed a new mechanism regulating the cleavage of Angpt2 that may explain the effects of Angpt2443 in the tumor environment. These findings help to explain the importance of Angpt2 protein domains in tumor growth and metastasis that could be utilized in the development of new cancer treatments.

 

Last updated: 23.10.2019