title: Upregulation of heat shock proteins and the promotion of damage-associated molecular pattern signals in a colorectal cancer model by modulated electrohyperthermia.
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.
authors: Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors: Gabor
authors: G
authors: Andocs
authors: Nora
authors: N
authors: Meggyeshazi
authors: Lajos
authors: L
authors: Balogh
authors: Sandor
authors: S
authors: Spisak
authors: Mate Elod
authors: ME
authors: Maros
authors: Peter
authors: P
authors: Balla
authors: Gergo
authors: G
authors: Kiszner
authors: Ivett
authors: I
authors: Teleki
authors: Csaba
authors: C
authors: Kovago
authors: Tibor
authors: T
authors: Krenacs
mesh_terms: D000818:Animals; D037282:Calreticulin / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000503:physiopathology*; D005455:Fluorescent Antibody Technique; D024243:HMGB1 Protein / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D006979:Hyperthermia, Induced; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012333:RNA, Messenger / Q000378:metabolism; D014183:Transplantation, Heterologous; D015854:Up-Regulation
chemical_list: D037282:Calreticulin; D024243:HMGB1 Protein; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D012333:RNA, Messenger