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Expression of complement protein C5a in a murine mammary cancer model: Tumor regression by interference with the cell cycle

Title
Expression of complement protein C5a in a murine mammary cancer model: Tumor regression by interference with the cell cycle
Authors
Kim D.-Y.Martin C.B.Soon N.L.Martin B.K.
Ewha Authors
이순남
SCOPUS Author ID
이순남scopus
Issue Date
2005
Journal Title
Cancer Immunology, Immunotherapy
ISSN
0340-7004JCR Link
Citation
Cancer Immunology, Immunotherapy vol. 54, no. 10, pp. 1026 - 1037
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
The C5a anaphylatoxin protein plays a central role in inflammation associated with complement activation. This protein is commonly regarded as one of the most potent inducers of the inflammatory response and a C5a peptide agonist was used as a molecular adjuvant. However, the full length C5a protein has not been tested as a potential tumor therapy. In this report, we describe the creation of a mini-gene construct that directs C5a expression to any cell of interest. Functional expression could be demonstrated in the murine mammary sarcoma, EMT6. When C5a expressing cells were injected into syngeneic mice, most C5a-expressing clones had significantly reduced tumor growth. Further characterization of a clone expressing low levels of C5a demonstrated that one-third of mice injected with this line had complete tumor regression. The mice whose tumors regressed were immune to subsequent challenge with unmodified EMT6 cells, suggesting that a component of the innate immune response can be used to augment adaptive immunity. Cellular analyses demonstrated that a significant difference in actual tumor cell number could be detected as early as day 10. A block in cell cycle progression was evident at all time points and high levels of apoptosis were observed early in the regression event. These data demonstrate that the complement protein C5a can play a significant protective role in tumor immunity. © Springer-Verlag 2005.
DOI
10.1007/s00262-005-0672-7
Appears in Collections:
의과대학 > 의학과 > Journal papers
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