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基质胶对癌症研究中生物分布研究的影响。

Influence of matrigel on biodistribution studies in cancer research.

作者信息

Wolf Markus

机构信息

Department of Radiopharmaceutical Chemistry, German Cancer Research Centre, Heidelberg, Germany.

出版信息

Pharmazie. 2008 Jan;63(1):43-8.

Abstract

Matrigel matrix is widely used for supporting tumour implantation. However, some tumour cells are unable to degrade matrigel matrix resulting in residual matrigel at the time point of the biodistribution study or therapy experiment. In vitro cell uptake of tumour affine compounds into tumour cells embedded in matrigel was compared with matrigel free tumour cells. Matrigel accumulation exceeded cellular uptake of the tumour affine peptides. This suggests that matrigel might have an influence on the acquired biodistribution data when it is still present at the time point of the study. A quantitation of residual matrigel in tumour explants fourteen days after tumour implantation with a matrigel-tumour cell mixture showed that the overall matrigel content in the case of MCF-7 and AR42J tumours was about 23%. In order to evaluate the extent of accumulation of compounds in matrigel, nude mice bearing either tumours, tumour-matrigel-mixtures or matrigel alone received intravenous injections of fluorophor tagged tumour specific peptides. Fluorescence microscopy of cryosectioned matrigel, matrigel-tumour mixtures and tumour explants showed that the labelled compounds were matrigel associated and tumour cell associated with a higher fluorescence intensity in matrigel. In summary, matrigel matrix can influence biodistribution studies. It leads to believe in a higher tumour accumulation. Therefore, either a number of control experiments or the separation of matrigel from the tumour is necessary in order to obtain correct biodistribution data.

摘要

基质胶被广泛用于支持肿瘤植入。然而,一些肿瘤细胞无法降解基质胶,导致在生物分布研究或治疗实验的时间点出现基质胶残留。将肿瘤亲和性化合物在体外对包埋于基质胶中的肿瘤细胞的摄取情况与无基质胶的肿瘤细胞进行了比较。基质胶的积累超过了肿瘤亲和性肽的细胞摄取。这表明,在研究时间点基质胶仍然存在时,它可能会对获得的生物分布数据产生影响。对用基质胶-肿瘤细胞混合物进行肿瘤植入14天后肿瘤外植体中残留基质胶的定量分析表明,在MCF-7和AR42J肿瘤的情况下,基质胶的总体含量约为23%。为了评估化合物在基质胶中的积累程度,分别给荷瘤裸鼠、肿瘤-基质胶混合物裸鼠或仅注射基质胶的裸鼠静脉注射荧光标记的肿瘤特异性肽。对基质胶、基质胶-肿瘤混合物和肿瘤外植体冰冻切片的荧光显微镜检查显示,标记的化合物与基质胶相关且与肿瘤细胞相关,在基质胶中的荧光强度更高。总之,基质胶会影响生物分布研究。这导致人们认为肿瘤积累更高。因此,为了获得正确的生物分布数据,需要进行一些对照实验或将基质胶与肿瘤分离。

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