Vascularity, perfusion rate and local tissue oxygenation of tumors derived from rus‐transformed fibroblasts

Tumors derived from ras-transformed rat fibroblasts were investigated in order to gain insight into possible interrelationships between oncogenic transformations and therapeutically relevant parameters of the metabolic micromilieu of solid tumors in vivo. Tumors grew in nude mice after injection of in vitro-passaged cells. Growth rates, early stages of angiogenesis, perfusion and tissue oxygenation were assessed. Compared with the parental cell line, both ras transformants grew very rapidly and exhibited an early onset of angiogenesis. Perfusion rates of one ras-transformed tumor line were similar to those of the parental tumors whereas reduced flow values were detected in tumors of the other rats line. The better perfused tumors exhibited more adequate tissue oxygen levels whereas reduced oxygen levels were obvious in the poorly perfused ras line. These results indicate that ras transformation alters therapeutically relevant parameters of the tumor micromilieu. However, the tumor phenotype cannot be predicted even if the transforming oncogene is known.