Hyperthermia increases the metastatic potential of murine melanoma

Abstract

Hyperthermia, either alone or combined with radio-, immuno-or chemotherapy, can control tumor growth, but its effect on metastasis is still controversial. In the present study, we investigated the influence of hyperthermia on the metastatic potential of B16-F10 murine melanoma cells. Incubation of melanoma cells at 43 o C for 30 min led to a significant decrease in cell viability. About half of the cells survived the acute exposure to heat. These thermoresistant cells displayed a longer lag phase as compared to control unheated B16-F10 melanoma cells. Other parameters of cell growth such as doubling time and saturation density were equivalent in both control and thermoresistant cells. Both control and treated cells were adherent, but thermoresistant cells failed to spread during the first 48 h after heat exposure. B16-F10 cells colonize the lungs of C57BL/6J mice when injected intravenously; the number of lung colonies is a measure of the metastatic potential of injected cells. Median values of 22, 10.5 and 31 colonies per injected mouse were observed for control cells, cells heated to 43 o C for 30 min and thermoresistant cells, respectively, with statistically significant differences between groups (Mann-Whitney test, P<0.02). Thus, despite its cytotoxic action, heat exposure induced the acquisition of a more metastatic phenotype in a subpopulation of B16-F10 cells.

Heat stress induces epithelial plasticity and cell migration independent of heat shock factor 1

“…This study examined an acute cellular response (24 h) following thermal ablation, whether the EMT phenotype observed in this study persists over time remains to be delineated. However, Oliveira-Filho and colleagues have previously demonstrated that hyperthermic treatment of murine B16-F10 melanoma cell lines, although having a short-term negative impact upon cell viability and metastatic lung colonisation in mice, cells that were allowed to recover and injected into mice 13 days following heat shock treatment displayed an enhanced metastatic propensity (Oliveira-Filho et al 1997). This points to a somewhat prolonged enhancement of metastatic phenotype induced by a single heat treatment.…”

Heating Preciosity—Trends in Modern Oncological Hyperthermia

“…The positive local response does not necessarily mirror the survival because metastatic potential could be increased. The high-energy heating could increase the blood flow, which promotes the dissemination [33] [34] [35] and could likely produce metastases. Promotion of metastases by hyperthermia was observed in laboratory heating experiments on mammary carcinomas in C3H mice [36], sarcoma in rats [37], and Yoshida tumours [38].…”

Local Hyperthermia in Oncology – To Choose or not to Choose?

“…The blood-flow will be enhanced, the nutrients supply will be higher and the result is the opposite of our aim. The situation becomes even worse by continuing the high-energy heating: the high blood-flow helps the dissemination [147], [148], [149] and could gain the metastases: Figure 11. With this, we can definitely worsen the survival and the quality of life of the patient.…”

Essentials of Oncothermia

“…This rapidly emerging period was shadowed by skeptic opponents, which emphasized the increased dissemination of the malignant cells and so supported metastases by hyperthermia [31][32][33]. Direct negative opinion was formulated about the mistakes of hyperthermia investigations [34]: "The mistakes made by the hyperthermia community may serve as lessons, not to be repeated by investigators in other novel fields of cancer treatment.…”

“Quo Vadis” Oncologic Hyperthermia?

“…From the standpoint of oncology, the official policy was to avoid applying hyperthermia in oncotherapies. The repulsive opinion focused on the increase of dissemination of malignant cells and so supporting the metastases [22][23][24]. There were also reports about the induced hepatitis by hyperthermia [25].…”