RT Journal Article
SR Electronic
T1 Identification of Serpin (α-1-Antitrypsin) as Serum Growth Inhibitory Factor in Murine Ehrlich Carcinoma by Proteomics
JF Cancer Genomics - Proteomics
JO Cancer Genomics Proteomics
FD International Institute of Anticancer Research
SP 147
OP 156
VO 7
IS 3
A1 F.V. DONENKO
A1 R.H. ZIGANSHIN
A1 N. YU. ANISIMOVA
A1 K.E. VOYUSHIN
A1 S.M. SITDIKOVA
A1 B.S. AMANDZHOLOV
A1 M.V. KISELEVSKII
A1 T. EFFERTH
YR 2010
UL http://cgp.iiarjournals.org/content/7/3/147.abstract
AB It is well established that serum factors play a role in relapse of tumor diseases after removal of the primary tumor. The molecular nature of these factors and their mechanism of action remain unknown. We focused on host-related mechanisms to identify tumor-specific serum factors of mice bearing Ehrlich carcinoma, which have the potential to confer resistance towards tumor development. An experimental model was used, where we incubated isolated immune cells (peritoneal cells (PCs) and splenic lymphocytes (SLCs)) in vitro with blood serum or ascitic fluid from tumor-bearing mice. Mice inoculated with PCs or SLCs previously incubated for 7 h with ascitic fluid from tumor-bearing mice did not develop tumors at a frequency of 93.1±5.7% (inoculation of tumor cells after two weeks) and 100% (inoculation of tumor cells three months later). This indicates that mice developed resistance towards tumor development. By fractionation of ascitic fluid and (LC/MS-MS)-driven profiling of serum proteins, we identified serpin (α-1-antitrypsin), which was missing from the PC-incubated fraction, indicating that this protein was bound to PCs and, thereby, purged from the protein fraction. In parallel, cathepsin L1 appeared after incubation with PCs. Serpins play a central role in the regulation of a wide variety of (patho)-physiological processes, including coagulation, fibrinolysis, inflammation, development, tumor invasion and apoptosis. Furthermore, serpins may protect parasites against the immune systems of the host. Taken together, it can be hypothesized that serpin represents a tissue- and tumor-specific anti-proteinase.