Upregulation of heat shock proteins and the promotion of damage-associated molecular pattern signals in a colorectal cancer model by modulated electrohyperthermia

Gabor Andocs, Nora Meggyeshazi, Lajos Balogh, Sandor Spisak, Mate Elod Maros, Peter Balla, Gergo Kiszner, Ivett Teleki, Csaba Kovago, Tibor Krenacs

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

In modulated electrohyperthermia (mEHT) the enrichment of electric field and the concomitant heat can selectively induce cell death in malignant tumors as a result of elevated glycolysis, lactate production (Warburg effect), and reduced electric impedance in cancer compared to normal tissues. Earlier, we showed in HT29 colorectal cancer xenografts that the mEHT-provoked programmed cell death was dominantly caspase independent and driven by apoptosis inducing factor activation. Using this model here, we studied the mEHT-related cell stress 0-, 1-, 4-, 8-, 14-, 24-, 48-, 72-, 120-, 168- and 216-h post-treatment by focusing on damage-associated molecular pattern (DAMP) signals. Significant cell death response upon mEHT treatment was accompanied by the early upregulation (4-h post-treatment) of heat shock protein (Hsp70 and Hsp90) mRNA levels. In situ, the treatment resulted in spatiotemporal occurrence of a DAMP protein signal sequence featured by the significant cytoplasmic to cell membrane translocation of calreticulin at 4 h, Hsp70 between 14 and 24 h and Hsp90 between 24- and 216-h post-treatment. The release of high-mobility group box1 protein (HMGB1) from tumor cell nuclei from 24-h post-treatment and its clearance from tumor cells by 48 h was also detected. Our results suggest that mEHT treatment can induce a DAMP-related signal sequence in colorectal cancer xenografts that may be relevant for promoting immunological cell death response, which need to be further tested in immune-competent animals.

Original languageEnglish
Pages (from-to)37-46
Number of pages10
JournalCell Stress and Chaperones
Volume20
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

Keywords

  • Calreticulin
  • Damage-associated molecular pattern
  • Heat shock protein
  • High-mobility group box1 protein
  • Modulated electrohyperthermia

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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