PDF(Pubmed)
Abstract：
BACKGROUND: The accuracy of blood-based early tumour recognition is compromised by signal production at non-tumoral sites, low amount of signal produced by small tumours, and variable tumour production. Here we examined whether tumour-specific enhancement of vascular permeability by the particular tumour homing peptide, iRGD, which carries dual function of binding to integrin receptors overexpressed in the tumour vasculature and is known to promote extravasation via neuropilin-1 receptor upon site-specific cleavage, might be useful to improve blood-based tumour detection by inducing a yet unrecognised vice versa tumour-to-blood transport.
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.
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.
摘要：
背景：基于血液的早期肿瘤识别的准确性受到非肿瘤部位信号产生的影响，小肿瘤产生的信号量低，和可变的肿瘤生产。在这里，我们检查了特定肿瘤归巢肽是否对血管通透性的肿瘤特异性增强，IRGD,它具有与在肿瘤脉管系统中过度表达的整合素受体结合的双重功能，并且已知在位点特异性裂解时通过神经纤毛蛋白1受体促进外渗，可能有助于通过诱导尚未识别的肿瘤到血液的运输来改善基于血液的肿瘤检测。
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。
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。
