Clinical significance of heat shock proteins in gastric cancer following hyperthermia stress: Indications for hyperthermic intraperitoneal chemoperfusion therapy

Abstract

Heat shock proteins (HSPs) are important factors in the response of cancer cells to thermo- and chemotherapy. Transient hyperthermic intraperitoneal chemoperfusion (HIPEC) therapy results in the upregulation of HSP expression, which may compromise the efficacy of additional anticancer treatments. The aim of the present study was to monitor the kinetics of HSP expression in tumor cells and patients with gastric cancer following HIPEC. Thus, and experiments were conducted to investigate the expression of two HSP family members, HSP70 and HSP90. Cells from two gastric tumor strains were subjected to HIPEC-mimicking treatment, and HSPs expression was analyzed at specific time points up to 48 h. Serum HSP concentrations were analyzed in patients with gastric cancer who had previously received cytoreductive surgery plus HIPEC treatment. The experiments indicated a significant elevation of HSP90 expression in gastric adenocarcinoma cells following hyperthermic treatment. However, HSP70 expression increased from 4 h up to 20 h post-exposure and decreased to normal levels 36 h post-exposure. Analysis of HSPs in serum samples collected from 22 patients with gastric cancer confirmed that serum HSP90 and HSP70 levels increased following HIPEC therapy, peaking at 18 h and returning to normal 24 h post-exposure. It is therefore advisable to apply the second round of HIPEC or chemotherapy at least 24 h following the first treatment to minimize any potential thermoresistance and chemoresistance of tumor cells.

The Treatment of Heterotopic Human Colon Xenograft Tumors in Mice with 5-Fluorouracil Attached to Magnetic Nanoparticles in Combination with Magnetic Hyperthermia Is More Efficient than Either Therapy Alone

“…The significantly reduced expression of the HSP90 (p < 0.05, day 28 post first tumor therapy) could be related to a high protein "consumption" of those tumor cells which were struggling for survival. It is of note that HSP70 and HSP90 are inducible molecular chaperons [51]. They exert a chaperoning role by refolding or targeting proteins for degradation [52], which have previously been damaged as a consequence of heat.…”

Hyperthermia During Intraperitoneal Chemotherapy With Paclitaxel or Docetaxel for Ovarian Cancer: Is There Any Benefit?

“…In a mouse melanoma model, hyperthermia seemed to cause immunosuppressive effects and subsequently disease progression (35). Moreover, the enhanced systemic release of heat-shock proteins (HSPs) during HIPEC may result in reduced response to hyperthermia as well as chemotherapy (36)(37)(38)(39)(40). Additionally, HSPs have anti-apoptotic properties and promote tumor cell proliferation, invasiveness and metastatic dissemination (39,41).…”

Increased temperature‑related adeno‑associated virus vectors transduction of ovarian cancer cells ‑ essential signatures of AAV receptor and heat shock proteins

“…Therefore, they perform regulatory functions in the fundamental biological processes such as proliferation, apoptosis, drug resistance, stress response (25–27). HSP signatures in cells are different, there are significant differences in the constitutive expression of HSP genes in tumor cells, which are associated with the pathomechanisms of cancer development (28,29). In ovarian cancers, the important role of HSP27, HSP70 and HSP90 is stressed (29).…”