Complement and cancer

Complement-dependent cytotoxicity is one of the mechanisms by which therapeutic monoclonal antibodies are toxic to cancer cells. Also, complement is currently undergoing re-appreciation of its role in the immune surveillance of tumors. The majority of human tumors are low immunogenic and complement may be involved in their recognition via direct “danger signal” elicited activation. This in turn attracts inflammatory cells that may be associated with malignant transformation but also with tumor regession. The experimental evidence is being accumulated to show opposing roles of complement in tumor control.

Therefore we investigate:

1. function of several poorly characterized proteins expressed in tumor cells and which are structurally related to known complement inhibitors but also suggested to act for example as tumor suppressor genes. One of these is CSMD1, a large transmembrane protein deleted in number of tumors but also acting as complement inhibitor. Another is SUSD4, which we recently showed to be complement inhibitor and which we found on cells infiltrating various solid tumors. We study how these proteins are related to tumor development in breast, prostate and melanoma cancer models.

2. how a complement regulator and extracellular matrix protein COMP (cartilage oligomeric matrix protein) affects certain types of cancer cells in which it is highly expressed and it if can be used as biomarker

3. Importance of complement activation and individual variations in complement levels for therapeutic effect of clinically approved anti-CD20 mAbs used for treatment of B cell malignancies.

SOURCE

http://www.med.lu.se/english/labmedmalmo/anna_blom_research_group/projects/complement_and_cancer