Heterogeneity of tumor oxygenation: relationship to tumor necrosis, tumor size, and metastasis

Relationship of hypoxia to metastatic ability in rodent tumours

“…Both tumour types, measured at tumour weight 0.3-0.4 g show variation within an almost identical range ( Figure 1A, B). This range is in agreement with our preliminary data (De Jaeger et al, 1998) and with data obtained in our lab in a different group of KHT-C tumours (Kavanagh et al, 1999). We have previously shown in KHT tumours that consecutive measurements of pO 2 in the same tumour give similar results and that there is a correlation in individual KHT tumours between measurements of pO 2 made when the tumours were 0.3-0.4 g and when they were 1.0-1.1 g in size (De Jaeger et al, 1998).…”

“…This range is in agreement with our preliminary data (De Jaeger et al, 1998) and with data obtained in our lab in a different group of KHT-C tumours (Kavanagh et al, 1999). We have previously shown in KHT tumours that consecutive measurements of pO 2 in the same tumour give similar results and that there is a correlation in individual KHT tumours between measurements of pO 2 made when the tumours were 0.3-0.4 g and when they were 1.0-1.1 g in size (De Jaeger et al, 1998). We and others have postulated that variation in pO 2 values, measured in individual tumours from the same cell line, at the same size and transplanted in identical hosts, are likely to be a consequence of differences associated with local tumour growth and stochastic development of vasculature rather than intrinsic genetic differences (Rockwell and Moulder, 1990;De Jaeger et al, 1998).…”

“…We have previously shown in KHT tumours that consecutive measurements of pO 2 in the same tumour give similar results and that there is a correlation in individual KHT tumours between measurements of pO 2 made when the tumours were 0.3-0.4 g and when they were 1.0-1.1 g in size (De Jaeger et al, 1998). We and others have postulated that variation in pO 2 values, measured in individual tumours from the same cell line, at the same size and transplanted in identical hosts, are likely to be a consequence of differences associated with local tumour growth and stochastic development of vasculature rather than intrinsic genetic differences (Rockwell and Moulder, 1990;De Jaeger et al, 1998). Similar heterogeneity in oxygenation, but over a wider range has been reported in human tumours (Gatenby et al, 1988;Höckel et al, 1993Höckel et al, , 1996Brizel et al, 1995Brizel et al, , 1996Brizel et al, , 1997Nordsmark et al, 1996;Fyles et al, 1998;Sundfør et al, 1998).…”

“…This graph is updated from previously reported preliminary results (De Jaeger et al, 1998). Although there seems to be a trend suggesting increasing incidence of lung metastases with increasing hypoxic fraction, there is only a weak, non-significant correlation (r s = 0.19, P = 0.25).…”

“…At a tumour weight 1.6-1.9 g, macroscopic metastases were present in the majority of the lungs with only 2/40 mice not showing macroscopically visible pulmonary metastases. As depicted in Figure 2A only a weak non-significant correlation was observed between oxygenation of the primary tumour at tumour weight 0.3-0.4 g and the number of lung metastases observed at weight 1.6-1.9 g. We hypothesized that a possible relationship could be obscured by the presence of massive lung metastases when the primary tumours reach a weight of 1.6-1.9 g and by the fact that the tumours become increasingly hypoxic as their weight increases above 0.3 g (De Jaeger et al, 1998). In a previous study (Hill et al, 1986) we showed that KHT-C fibrosarcoma starts seeding metastases into the lungs at a tumour weight of 0.25 g (corresponding leg diameter = 7.5-8 mm).…”