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PMID: 18463535 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Low-dose chemotherapeutic agents regulate small Rho GTPase activity in dendritic cells.

Journal of immunotherapy (Hagerstown, Md. : 1997) ·Vol. 31 ·No. 5 ·2008-06-00 ·Pages 491-9

Shurin GV, Tourkova IL, Shurin MR

Abstract

Conventional chemotherapy targets dividing tumor cells and might support antitumor immunity by providing tumor antigens from dying tumor cells to antigen-presenting dendritic cells (DCs). Despite emerging evidence to suggest that phagocytosis of dying tumor cells by DCs requires membrane targeting of specific small Rho guanosine triphosphatases (GTPases), nothing is known with regard to the direct effect of chemotherapeutic agents on low molecular weight Rho GTPases in DCs. Prompted by a recent observation that low-dose chemotherapeutic drug paclitaxel could up-regulate DC maturation and function, here we studied putative regulatory roles for various chemotherapeutic agents in modulating small Rho GTPases in DC. Our results demonstrate that different classes of chemotherapeutic drugs at low nontoxic concentrations regulate activity of Rac, RhoA, and RhoE in murine DC, suggesting that small Rho GTPases might serve as new targets for modulating functional activity of DC vaccines or endogenous DCs in various immunotherapeutic or chemoimmunotherapeutic strategies.

MeSH Terms
Animals Antineoplastic Agents/administration & dosage,pharmacology Cells, Cultured Dendritic Cells/drug effects,enzymology Enzyme Activation/drug effects Male Mice rho GTP-Binding Proteins/metabolism
Chemicals
Antineoplastic Agents rho GTP-Binding Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Shurin Galina V
Department of Pathology, Division of Clinical Immunopathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA. [email protected]
Tourkova Irina L
Shurin Michael R
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Article Info
Journal
Journal of immunotherapy (Hagerstown, Md. : 1997)
Abbr.
J Immunother
ISSN
1524-9557
DOI
10.1097/CJI.0b013e318176fae4
Email
[email protected]
Published
2008-06-00
Pages
491-9
Language
English
Region
United States
NLM ID
9706083
PMCID
PMC4001709
Subset
IM
Grants
NCI NIH HHS · R01 CA084270 · United States
NCI NIH HHS · 2 R01 CA 84270 · United States
External Links
PubMed source DOI: 10.1097/CJI.0b013e318176fae4 PMC Full Text View journal details
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