Biochemical and Biophysical Research Communications
Release of endogenous danger signals from HIFU-treated tumor cells and their stimulatory effects on APCs
Section snippets
Materials and methods
Cell cultures. RAW264.7 mouse macrophage cell line was obtained from American Type Culture Collection (Manassas, VA). The MC-38 mouse colon adenocarcinoma tumor cell line was kindly provided by Dr. Jeffrey Schlom of NCI (Bethesda, MD). Cell lines were maintained in complete Dulbecco’s modified Eagle’s medium (DMEM), supplemented with 10% heat-inactivated fetal bovine serum (FBS) (Gibco, USA) at 37 °C and 5% CO2. Tumor cells used in the experiments were in log-phase with 24 h doubling time. Before
Thermal and mechanical lysis of the tumor cells produced by a HIFU transducer
Current HIFU therapy is focused almost exclusively on producing thermal ablation of the tumor tissues. However, both thermal and mechanical damage may be caused by HIFU through heat impulse and acoustic cavitation. Here, we compared the HIFU-induced damage of MC-38 tumor cells using two different exposure strategies, with one emphasizing the thermal effect but the other emphasizing the mechanical effect produced by the same 1.1 MHz HIFU transducer under different output conditions. The acoustic
Discussion
Using tumor cell line MC-38, we have demonstrated in vitro that HIFU treatment can cause both thermal and mechanical necrosis, leading to the release of endogenous danger signals (ATP and hsp60) from the damaged tumor cells. We have further demonstrated that the released danger signals can stimulate the maturation of APCs, such as DCs and macrophages. Most importantly, the immuno-stimulatory effect of mechanically lysed tumor cells was found to be much stronger than that of thermally ablated
Acknowledgment
This work was supported in part by NIH Grant No. RO1-EB02682.
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