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Mechanism of Metastatic Spread by 42°C Total-Body Hyperthermia in Lewis Lung Carcinoma¹

First Department of Surgery, Tottori University School of Medicine, 36-1 Nishimachi, Yonago 683, Japan

We investigated the mechanism of metastatic spread in Lewis lung carcinoma-bearing C57BL/6 mice exposed to 42°C total-body hyperthermia (TBH) by water immersion. When the mice were treated with 42°C TBH 24 h after resection of the primary tumor, the spread of lung metastasis was inhibited (P < 0.01). When tumor-bearing mice were exposed to 42°C TBH followed by resection of the primary tumors 24 h later, the spread of lung metastasis was greater than in the control group from which tumors were removed 6 days after inoculation (P < 0.05). When normal mice were subjected to 42°C TBH and Lewis lung carcinoma cells were subsequently injected i.v., lung metastasis increased significantly in those mice that had received tumor cell injection between immediately after and 48 h after TBH treatment (P < 0.02–0.001). Tumor-bearing mice were subjected to 42°C TBH, and changes in the lung tissues were examined. Between 12 and 48 h after TBH, alveolar collapse, edema, and cellular infiltration into the alveolar walls were seen. Tumor-bearing mice were exposed to 42°C TBH and blood was taken from the inferior vena cava. The number of tumor cells in the blood increased significantly 12 h after TBH exposure (P < 0.05). We suggest that TBH promotes the intravascular invasion of tumor cells and that histological changes in the host lung facilitate the implantation of tumor cells.

¹ Supported by a grant-in-aid for cancer research from the Japanese Ministry of Education and Culture (1982, 1983).

² To whom requests for reprints should be addressed.

Received 3/19/85. Revised 7/15/85. Revised 11/ 4/85. Accepted 11/22/85.