The complement system plays major roles in innate and adaptive immunity. Complement activation may proceed through the classical, lectin and alternative pathways that initiate assembly of the membranolytic C5b-9 complex, also known as the membrane attack complex or MAC. Insertion of the C5b-9 complex into target cells membrane is an important weapon the body uses to fight pathogenic microorganisms. However, in many diseases, the C5b-9 complexes are considered pathogenic and inflict damages to patients' organs. During antibody-based therapy, complement C5b-9 complexes penetrate the plasma membrane of antibody-coated cancer cells and facilitate cancer destruction and remission. Several resistance mechanisms protect cancer cells from complement-dependent cytotoxicity. We found that the mitochondrial hsp70 mortalin supports cancer evasion from cell death activated by C5b-9. The mechanism whereby mortalin is protecting cells is currently under investigation. Initial results indicate that mortalin promotes C5b-9 elimination from the cell surface. The plausible target proteins recognized by mortalin are the C8 and C9 components of the C5b-9 complex. Since mortalin expression is elevated in cancer, it is conceivable that mortalin poses an obstacle to antibody-based therapy and as such might be worth targeting.
|Title of host publication||Mortalin Biology|
|Subtitle of host publication||Life, Stress and Death|
|Number of pages||9|
|ISBN (Print)||9400730268, 9789400730267|
|State||Published - 1 Apr 2014|