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Review
. 2013 May 16;4(5):e631.
doi: 10.1038/cddis.2013.156.

Many faces of DAMPs in cancer therapy

O Krysko  1 , T Løve Aaes, C Bachert, P Vandenabeele, D V Krysko
Affiliations
Review

Many faces of DAMPs in cancer therapy

O Krysko et al. Cell Death Dis. .

Abstract

A new concept of immunogenic cell death (ICD) has recently been proposed. The immunogenic characteristics of this cell death mode are mediated mainly by molecules called 'damage-associated molecular patterns' (DAMPs), most of which are recognized by pattern recognition receptors. Some DAMPs are actively emitted by cells undergoing ICD (e.g. calreticulin (CRT) and adenosine triphosphate (ATP)), whereas others are emitted passively (e.g. high-mobility group box 1 protein (HMGB1)). Recent studies have demonstrated that these DAMPs play a beneficial role in anti-cancer therapy by interacting with the immune system. The molecular pathways involved in translocation of CRT to the cell surface and secretion of ATP from tumor cells undergoing ICD are being elucidated. However, it has also been shown that the same DAMPs could contribute to progression of cancer and promote resistance to anticancer treatments. In this review, we will critically evaluate the beneficial and detrimental roles of DAMPs in cancer therapy, focusing mainly on CRT, ATP and HMGB1.

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Figures

Figure 1
Figure 1
DAMPs are derived from different compartments of the cells. For example, they can come from mitochondria (DNA, formyl peptides and ATP), nucleus (HMGB1, high-mobility group box 1 protein; HMGN1, high mobility group nucleosome binding protein 1; histones), ER (calreticulin and ATP) and cytoplasm (ATP and F-actin), ,
Figure 2
Figure 2
ATP is actively secreted by dying tumor cells in the early apoptotic stage and could be involved in pro- and anti-tumorigenic activities
Figure 3
Figure 3
Passive release of HMGB1 from the nucleus of tumor cells during the late stages of apoptotis (e.g. secondary necrosis) induces both pro- and anti-tumorigenic activities, which may depend on the redox state of HMGB1. The redox states are indicated by SH (fully reduced), S-S (disulfide bonds), SO3H (oxidized) and ★ (unknown)
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