ABSTRACT: To investigate the direct relationship between tumour hypoxia and lactate dehydrogenase (Ldh) levels in serum and tumour in two different pre-clinical murine models.
Experiments were performed in CDF1 or C3H/ Km mice implanted with a C3H mammary carcinoma and SCCVII squamous cell carcinoma, respectively. Low oxygen breathing for 1-72 h was used to increase tumour hypoxia. Ldh activity was measured in the serum and tumour cytosole with a colorimetric method. Tumour Ldha mRNA levels were assessed with RT-PCR. RESULTS; The serum Ldh in non-tumour bearing CDF1 mice and C3H/km mice was 10.592 U/ml and 1292 U/ml, respectively. For C3H mammary carcinoma bearing mice, a positive correlation between tumour volume and tumour and serum Ldh was found. Tumour Ldh in SCCVII carcinomas also increased with increasing tumour volume, but no volume dependence of serum Ldh was found. Low oxygen breathing caused a 2-3 fold increase in tumour Ldha mRNA in both tumour models. In C3H mammary carcinoma bearing mice, serum and tumour Ldh significantly increased after 48 and 72 hours of hypoxia, respectively. Low oxygen breathing did not change serum and tumour Ldh in SCCVII carcinoma bearing mice. Reoxygenation for 4 or 24 hours had no additional effect on Ldh activity in any of the models.
Serum Ldh activity can be a marker for tumour burden in certain types of cancer. The relationship between serum and tumour Ldh and tumour hypoxia has not been confirmed. However, Ldha mRNA may be a potential new marker of tumour hypoxia and should be further investigated.
Acta oncologica (Stockholm, Sweden) 02/2008; 47(5):941-7. · 2.27 Impact Factor
ABSTRACT: To investigate the relationship between tumour hypoxia and serum and tumour osteopontin (OPN) levels.
Experiments were performed in CDF1 or C3H/Km mice implanted with a C3H mammary carcinoma (CDF1) or SCCVII squamous cell carcinoma (C3H/Km), respectively. Mice were either untreated or gassed with 10% oxygen for 1-72 h. Serum and tumour OPN levels were measured with an ELISA and tumour OPN mRNA levels using RT-PCR. Tumour oxygenation was estimated using the Eppendorf histograph with the percentage of pO(2) values <or=5 mm Hg (HF5) as the endpoint.
OPN levels were 50-fold higher in the serum of non-tumour bearing CDF1 mice compared to C3H/Km mice. A tumour related increase in serum OPN levels was observed in CDF1 but not in C3H/Km mice. Low oxygen breathing increased HF5 in both tumour models and in the C3H mammary carcinoma model both serum and tumour OPN decreased after prolonged hypoxia (24h and more). When 12h of hypoxia was followed by 24h reoxygenation there was a twofold increase in serum OPN levels. No changes were observed in the SCCVII model. No changes in tumour OPN mRNA expression were observed during hypoxia and reoxygenation in these tumour models.
Clear strain and tumour specific differences in the effect of hypoxia on OPN levels have been observed in two different mouse tumour models. These data emphasize the complexity in the relationship between poor oxygenation (and/or reoxygenation) of tumours and serum levels of OPN.
Radiotherapy and Oncology 08/2006; 80(2):165-71. · 5.58 Impact Factor
ABSTRACT: To investigate the possible relationship between radiobiological hypoxia in a C3H mouse mammary carcinoma and osteopontin (OPN) levels measured in mouse serum.
Experiments were performed in CDF1 mice that were either non-tumour bearing or with different sized tumours implanted in the right rear foot. Osteopontin levels in extracted mouse blood serum and tissue from the transplanted tumours were measured using an ELISA assay. The tumour oxygenation status was estimated using the Eppendorf Histograph and the fraction of oxygen partial pressure (pO2) values =5 mm Hg (HF5) was calculated. Necrosis was measured in haematoxylin and eosin-stained sections. Tumour hypoxia was increased by placing animals in a low-oxygen (10%) environment. Single radiation doses (240 kV x-rays) were given locally to tumours under ambient or clamped conditions and response assessed using a tumour control assay.
Serum OPN levels increased linearly with increasing tumour volume and this increase correlated with tumour OPN. HF5 and necrosis also increased with increasing tumour volume, but this increase was non-linear. Converting the HF5 results into equivalent tumour volume gave results that were directly correlated to OPN serum levels. Placing mice in a 10% oxygen environment for 12 hours significantly increased HF5. However, serum OPN only increased if reoxygenation occurred before measurement. Radiobiological hypoxic fraction in this tumour model did not change with increasing tumour size, but the total number of hypoxic cells did increase.
These findings suggest that serum OPN measurement may predict the proportion of hypoxic cells in this tumour model, although increased serum OPN levels simply resulting from an increased tumour burden can not be ruled out.
International Journal of Radiation Biology 01/2006; 81(12):937-44. · 2.28 Impact Factor