Hyperthermic Intraperitoneal Chemotherapy in Patients with Peritoneal Carcinomatosis: Role of Heat Shock Proteins and Dissecting Effects of Hyperthermia

Joerg O. W. Pelz, Malte Vetterlein,, Tanja Grimmig,, Alexander G. Kerscher, Eva Moll,, Maria Lazariotou,, Niels Matthes,, Marc Nicolas Faber, Christoph-Thomas Germer,, Ana Maria Waaga-Gasser,, Martin Gasser,

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background:
In patients with isolated peritoneal carcinomatosis (PC) of gastrointestinal cancer, hyperthermic intraperitoneal chemotherapy (HIPEC) represents a promising treatment option integrated into multimodal concepts. Heat shock proteins (HSP) seem to play a major role in cellular stress during HIPEC therapy. We analyzed differentially hyperthermic conditions and HSPs responsible for cell stress-mediated repair mechanisms in tumor tissues from patients who underwent HIPEC therapy and in an in vitro hyperthermic model.

Methods:
Tumor tissues from our patient cohort with isolated PC were selected for further analysis when representative material was available before and after HIPEC therapy. To further dissect the role of HSPs under conditions of hyperthermia, gene and protein expression was additionally determined, together with cellular apoptosis and proliferation in human HT-29 colon cancer cells.

Results:
Differently up-regulated HSP70/72 and HSP90 gene and protein expression was found in all investigated patient tumors. In vitro studies confirmed observations from clinical tumor analysis as underlying HSP-mediated cell stress mechanisms. Moreover, results from proliferation and apoptosis assays combined with differentiated HSP expression analysis demonstrated the relevance of preselecting specific target temperatures to achieve optimal toxic effects on remaining tumor cells in vivo.

Conclusions:
Therapeutic approaches like HIPEC to achieve antiproliferative and apoptosis-inducing cellular effects in patients with PC are negatively influenced by highly conserved HSP mechanisms in tumor cells. This study shows for the first time that specific hyperthermic conditions are necessary to be established to achieve optimal toxic effects on tumor cells during HIPEC therapy, a finding that opens potentially new therapeutic strategies.
Original languageEnglish
Pages (from-to)1105-1113
Number of pages9
JournalAnnals of Surgical Oncology
Volume20
Issue number4
Early online date2 Mar 2013
DOIs
Publication statusPublished - Apr 2013

    Fingerprint

Cite this