Identification of serpin (alpha-1-antitrypsin) as serum growth inhibitory factor in murine ehrlich carcinoma by proteomics.

Publication type:
Journal article
Metadata:
Abstract
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 (alpha-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.
Addresses
  • N.N. Blokhin Russian Cancer Research Center, Moscow, Russia.
Autoren
  • FV Donenko
  • RH Ziganshin
  • N Yu Anisimova
  • KE Voyushin
  • SM Sitdikova
  • BS Amandzholov
  • MV Kiselevskii
  • T Efferth
eISSN
1790-6245
Externe Identifier
  • PubMed Identifier: 20551247
Open access
false
ISSN
1109-6535
Ausgabe der Veröffentlichung
3
Zeitschrift
Cancer genomics & proteomics
Schlüsselwörter
  • Lymphocytes
  • Ascitic Fluid
  • Animals
  • Mice, Inbred C57BL
  • Mice
  • Carcinoma, Ehrlich Tumor
  • alpha 1-Antitrypsin
  • Proteomics
  • Apoptosis
  • Male
Sprache
eng
Medium
Print
Paginierung
147 - 156
Datum der Veröffentlichung
2010
Status
Published
Datum der Datenerfassung
2010
Titel
Identification of serpin (alpha-1-antitrypsin) as serum growth inhibitory factor in murine ehrlich carcinoma by proteomics.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
7

Data source: Europe PubMed Central

Other metadata sources:
Abstract
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 (alpha-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.
Autoren
  • FV Donenko
  • RH Ziganshin
  • N Yu Anisimova
  • KE Voyushin
  • SM Sitdikova
  • BS Amandzholov
  • MV Kiselevskii
  • T Efferth
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/20551247
eISSN
1790-6245
Ausgabe der Veröffentlichung
3
Zeitschrift
Cancer Genomics Proteomics
Schlüsselwörter
  • Animals
  • Apoptosis
  • Ascitic Fluid
  • Carcinoma, Ehrlich Tumor
  • Lymphocytes
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Proteomics
  • alpha 1-Antitrypsin
Sprache
eng
Country
Greece
Paginierung
147 - 156
PII
7/3/147
Datum der Veröffentlichung
2010
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2010
Titel
Identification of serpin (alpha-1-antitrypsin) as serum growth inhibitory factor in murine ehrlich carcinoma by proteomics.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
7

Data source: PubMed

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