Relationship between heat-induced vascular damage and thermosensitivity in four mouse tumors

The relationship between heat-induced vascular damage and thermosensitivity was studied using four mouse transplantable tumors. The tumors used were spontaneous mammary carcinoma, SCC VII carcinoma, EMT6 sarcoma, and B16 melanoma. Under cultured conditions, B16 was more thermosensitive at 43 degrees C and 44 degrees C than SCC VII or EMT6. The in vivo tumor response to heat was evaluated by the growth delay after heating at 44 degrees C for 30 min. Among the four tumors, SCC VII was the most thermosensitive in vivo followed by EMT6, whereas B16 and spontaneous mammary carcinoma were thermoresistant. Vascular damage was studied quantitatively up to 24 h after heating by using microangiography. The order of the four tumors in vascular damage was well correlated with the tumor response in vivo. Histologically, tumor vessels of spontaneous mammary carcinoma were supported by connective tissues, and those of B16 had dense endothelial cells, compared to sparse endothelial cells of SCC VII and EMT6. Our findings suggest that variability in heat sensitivity of tumors is related to variation in the histological structure of tumor vasculature. That is, tumor vasculature with perivascular connective tissues and/or dense endothelial cells is less heat labile than that composed only of sparse endothelial cells.