Tumour thermotolerance, a physiological phenomenon involving vessel normalisation

Abstract

The purpose of this study was to delineate the mechanisms by which stromal components of cancer may induce tumour thermotolerance and exploit alterations in stromal and tumour physiology to enhance radiation therapy. The vascular thermoresponse was monitored by daily one-hour 41.5°C heatings in two murine solid tumour models, SCK murine mammary carcinoma and B16F10 melanoma. A transient increase was seen in overall tumour oxygenation for 2–3 days, followed by a progressive decline in tumour pO2 upon continued daily heatings. Vascular thermotolerance was further studied by treating tumours with different heating strategies, i.e. (1) a single 60 min 41.5°C treatment; (2) two consecutive daily treatments of 41.5°C for 60 min; (3) a single 60 min 43°C treatment or (4) two days of 41.5°C for 60 min followed by treatment with 43°C for 60 min on the third day. Pre-heating tumours with mild temperature hyperthermia induced vascular thermotolerance, which was accompanied by evidence of vessel normalisation, i.e. a decrease in microvessel density and an increase in pericyte coverage. Rational scheduling of fractionated radiation during heat-induced increases in tumour oxygen levels rendered a significantly greater, synergistic, tumour growth inhibition. In vitro clonogenic survival responses of the individual cell types associated (endothelial cells, fibroblasts, pericytes and tumour cells) indicated only a direct cellular thermotolerance in endothelial cells. Overall, this suggests that tumour thermotolerance is a physiological phenomenon mediated through improvement of functional vasculature.

In situ forming implants for local chemotherapy and hyperthermia of bone tumors

“…It also induced a significant vascular permeability increase in rats, which may explain plasma fluid shift into the interstitium [65,144]. Furthermore, more recently thermotolerance was correlated to a normalization of tumor vessels [145]. In contrast to these observations, and mostly below the threshold of 42-43°C, which corresponds more closely to the clinical temperature usually achieved, TBF seemed to be increased [65,140], probably allowing to achieve a higher drug delivery within the tumor tissues.…”

Polycationic calixarene PTX013, a potent cytotoxic agent against tumors and drug resistant cancer

“…HUVEC and fibroblasts were cultured in gelatin-coated tissue-culture flasks (0.2 %) in culture medium [RPMI 1640 with 20 % (v/v) human serum, supplemented with 2 mM glutamine, 100 units/mL penicillin and 0.1 mg/mL streptomycin]. Murine cell lines: endothelial (2H11), melanoma (B16F10), mammary carcinoma (SCK), and fibrosarcoma (FSAII) were kindly provided by Prof. Dr. R. Griffin [5, 13, 14] and human cell lines: lung carcinoma (A549), head and neck carcinoma (SQ20B), breast adenocarcinoma (MCF- 7), and colon adenocarcinoma (Colo205 and DLD-1) were obtained from ATCC (Rockville, MD, USA) or National Cancer Institute collection (Bethesda, MD, USA). The resistant SQ20B-R cell line was developed from the head and neck SQ20B cancer cell line by inducing acquired resistance to PTX008.…”

Effects of Thermotherapy on Th1/Th2 Cells in Esophageal Cancer Patients Treated with Radiotherapy

“…Thermotherapy targets cell membrane and cytoskeleton, while radiotherapy targets DNA, so the combined treatment can exert synergistic effect from different mechanisms (Saga et al, 2002;Bottaro and Liotta, 2003;Griffin et al, 2010;Dings et al, 2011). Heating can ameliorate the hypoxia status of tumor cells.…”