Relationship of hypoxia to metastatic ability in rodent tumours

The relationship between tumour oxygenation in vivo and metastatic potential was investigated in 2 rodent tumour models, KHT-C fibrosarcoma and SCC-VII squamous cell carcinoma. The oxygen status in these rodent tumours transplanted intramuscularly in syngeneic mice was measured using the Eppendorf pO(2)Histograph. The results indicate a considerable heterogeneity in oxygenation between individual tumours within each tumour cell line. At different tumour sizes, animals were killed and lung lobes were examined for macroscopic and microscopic lung metastases. In the KHT-C tumours, a significant increase in early pulmonary metastasis formation was observed in mice with hypoxic primary tumours. Hypoxic SCC-VII tumours did not give rise to enhanced lung metastasis formation despite oxygenation in a range similar to the KHT-C tumours. However, the overall metastasis incidence in the SCC-VII model was very low. The results obtained in the KHT-C model, which show that hypoxic tumours are more likely to metastasize, are in agreement with recent clinical data suggesting that a hypoxic environment might be implicated in metastatic ability of human tumours.