METHODS: To detect an iRGD-induced tumour-to-blood transport, we examined the effect of intravenously injected iRGD on blood levels of α-fetoprotein (AFP) and autotaxin in several mouse models of hepatocellular carcinoma (HCC) or in mice with chronic liver injury without HCC, and on prostate-specific antigen (PSA) levels in mice with prostate cancer.
RESULTS: Intravenously injected iRGD rapidly and robustly elevated the blood levels of AFP in several mouse models of HCC, but not in mice with chronic liver injury. The effect was primarily seen in mice with small tumours and normal basal blood AFP levels, was attenuated by an anti-neuropilin-1 antibody, and depended on the concentration gradient between tumour and blood. iRGD treatment was also able to increase blood levels of autotaxin in HCC mice, and of PSA in mice with prostate cancer.
CONCLUSIONS: We conclude that iRGD induces a tumour-to-blood transport in a tumour-specific fashion that has potential of improving diagnosis of early stage cancer.
BACKGROUND: Deutsche Krebshilfe, DKTK, LOEWE-Frankfurt Cancer Institute.
方法:为了检测iRGD诱导的肿瘤到血液的转运,我们检查了静脉注射iRGD对几种肝细胞癌(HCC)小鼠模型或无HCC的慢性肝损伤小鼠血液中甲胎蛋白(AFP)和自体运动因子水平的影响。和前列腺癌小鼠的前列腺特异性抗原(PSA)水平。
结果:静脉注射iRGD在几种HCC小鼠模型中迅速而有力地升高了AFP的血液水平,但在慢性肝损伤小鼠中没有。这种效应主要见于小肿瘤和正常基础血AFP水平的小鼠,被一种抗神经纤毛蛋白-1抗体减毒,取决于肿瘤和血液之间的浓度梯度。iRGD治疗也能够增加肝癌小鼠的自体运动因子的血液水平,和前列腺癌小鼠的PSA。
结论:我们得出结论,iRGD以肿瘤特异性方式诱导肿瘤到血液的转运,具有改善早期癌症诊断的潜力。
背景:德意志克雷贝希夫,DKTK,LOEWE-法兰克福癌症研究所。