|Cancer||Cell death||Cell cycle||Cytoskeleton||Exo/endocytosis||Differentiation||Division||Organelles||Signalling||Stem cells||Trafficking|
Cell Biology International (2008) 32, 835840 (Printed in Great Britain)
The effect of vaccination with the lysate of heat-shocked tumor cells on nitric oxide production in BALB/c mice with fibrosarcoma tumor
Seyed Mahmoud Hashemia, Zuhair M. Hassana*, Sara Soudia and Shahram Shahabib
aDepartment of Immunology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
bDepartment of Microbiology, Immunology and Genetics, Urmia University of Medical Sciences, Urmia, West Azarbaijan, Iran
The aim of this study was to investigate the effect of heat shock protein-70 (HSP-70) on splenocyte proliferation and nitric oxide (NO) production in the BALB/c mice fibrosarcoma tumor model. To do so, HSP-70 was induced in the lysate of heat-shocked tumor cells and WEHI-164 cells (mouse fibrosarcoma cell line) were injected subcutaneously into the right flank of inbred BALB/c mice to establish a tumor model. Three animal bearing tumor groups were applied: the test group; vaccinated with HSP-70 enriched tumor lysate; control group I, vaccinated with tumor lysate only; and control group II, which received PBS. Using immunoblot analysis, an increase of HSP-70 expression was detected in the lysate of heat-shocked cells in comparison with non-heat-shocked cells. The effect of the test lysate on NO production was measured both in vitro and in vivo in the peritoneal macrophages and splenocytes of tumor bearing mice, respectively. The result showed a significant increase in NO production both in vitro by peritoneal macrophages and in vivo after immunization with HSP-70 enriched tumor lysate. In addition, tumor growth was significantly postponed and the proliferation of splenocytes was increased in the test group. Our results indicate that the lysate of heat-shocked tumor cells was more potent than that of non-heat-shocked tumor cells in inducing anti-tumor immunity. Since production of NO by HSP-activated antigen presenting cells (APCs) is likely to affect innate immunity and tumor growth, the probable mechanism of postponing tumor growth would be NO production by innate immune cells. These findings provide a useful therapeutic model for developing novel approaches to cancer treatments.
Key words: Heat shock proteins, HSP-70, Nitric oxide, Cancer immunotherapy, Fibrosarcoma, Tumor cell lysate.
*Corresponding author. Department of Immunology, School of Medical Sciences, Tarbiat Modares University, P.O. Box 14115 111, Tehran, IR Iran. Tel.: +98 21 88011001x3565; fax: +98 21 88006544.
Received 26 September 2007/14 November 2007; accepted 26 March 2008doi:10.1016/j.cellbi.2008.03.014