Novel complement regulatory mechanisms in disease
Författare
Summary, in English
Sushi Domain-Containing Protein 4 (SUSD4) is a poorly studied human protein. We show that SUSD4 is a novel complement inhibitor that interferes with the formation of the C3 converts. Additionally, we found that SUSD4 is expressed by breast cancer cells, and that this expression is correlated with a better patient prognosis.
Factor I is a well-known complement inhibitor involved in the degradation of the activation products C4b and C3b. We detected factor I expression in breast cancer, and determined that breast cancer cells are able to produce the proteolytically active form of this protein. Analysis of patient data revealed that factor I expression correlates with poor survival rates.
Cartilage Oligomeric Matrix Protein (COMP) is a large protein involved in the organisation of collagen in the extracellular matrix. We have previously shown that it can both activate and inhibit the complement system. Here, we determined that COMP expression is unregulated in breast cancer tissue where it contributes to a more aggressive form of cancer. COMP expression correlates with poor prognosis and faster recurrence of the disease. Tumors expressing COMP, grown in vivo, were significantly larger and more invasive as compared to control tumors. Interestingly, COMP affected the metabolism and protein processing machinery of the cancer cells, helping them adapt better to a harsh environment.
In summary, this thesis describes novel, disease-related, functions of three complement regulators.
Avdelning/ar
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Proteinkemi, Malmö
Publiceringsår
2015
Språk
Engelska
Publikation/Tidskrift/Serie
Lund University Faculty of Medicine Doctoral Dissertation Series
Volym
2015:100
Dokumenttyp
Doktorsavhandling
Förlag
Department of Medical protein chemistry
Ämne
- Immunology in the medical area
- Cell and Molecular Biology
Status
Published
Forskningsgrupp
- Protein Chemistry, Malmö
Handledare
- Anna Blom
- Marcin Okroj
- Karin Jirström
ISBN/ISSN/Övrigt
- ISSN: 1652-8220
- ISBN: 978-91-7619-179-8
Försvarsdatum
27 november 2015
Försvarstid
09:00
Försvarsplats
Medelhavet, Wallenberg laboratory, Skånes Universitetssjukhus, Malmö
Opponent
- Michael Kirschfink (Prof)