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在fos基因转染的高转移性大鼠3Y1细胞系中,高侵袭性与运动性增强相关。

High invasiveness associated with augmentation of motility in a fos-transferred highly metastatic rat 3Y1 cell line.

作者信息

Taniguchi S, Tatsuka M, Nakamatsu K, Inoue M, Sadano H, Okazaki H, Iwamoto H, Baba T

机构信息

Department of Experimental Cell Research, Kyushu University, Fukuoka, Japan.

出版信息

Cancer Res. 1989 Dec 1;49(23):6738-44.

PMID:2684397
Abstract

We previously reported that v-fos transfer to a src-transformed rat 3Y1 cell line enhanced lung metastasis. To clarify the mechanism of this enhancement, we compared various biological factors related to metastatic potential between a fos-transferred highly metastatic cell line (fos-SR-3Y1-202) and the control cell line transferred with genetic marker (pSV2-neo) plus pBR322, neo-SR-3Y1-200. Lung arrest, the effect of lung extract on cell growth, or sensitivity to natural killer cells could not explain the higher metastasis of fos-SR-3Y1-202, compared to findings with neo-SR-3Y1-200. The invasiveness, assessed by penetration through a Matrigel-coated filter was about 5 times higher in fos-SR-3Y1-202 than in neo-SR-3Y1-200; high invasiveness in vitro was also observed in a fos-transferred mixed-population cell line (fos-SR-3Y1-200) and fos-transferred highly metastatic clones. Histopathological evidence of an in vivo tumor also showed the high invasiveness of fos-SR-3Y1-202 cells. To elucidate the causes of the increased invasiveness of fos-SR-3Y1-202, attachment of the cells to Matrigel and its components, such as laminin and type IV collagen, type IV collagenase activity, and motility were examined. Attachment of the cells to the substrate coated on Petri dishes or the activity of type IV collagenase did not differ significantly. On the other hand, cell motility, determined by a new method to directly quantitate alteration of cell shape continuously, using video image analysis and computer techniques, was higher in fos-SR-3Y1-202 than in neo-SR-3Y1-200. Thus, the fos-transferred cell line, fos-SR-3Y1-202 has a high invasiveness, in association with augmentation of motility, hence the enhancement of metastatic potential.

摘要

我们之前报道过,将v-fos转移至src转化的大鼠3Y1细胞系可增强肺转移。为阐明这种增强作用的机制,我们比较了fos转移的高转移性细胞系(fos-SR-3Y1-202)与转染了基因标记(pSV2-neo)加pBR322的对照细胞系(neo-SR-3Y1-200)之间各种与转移潜能相关的生物学因素。与neo-SR-3Y1-200的结果相比,肺滞留、肺提取物对细胞生长的影响或对自然杀伤细胞的敏感性均无法解释fos-SR-3Y1-202的更高转移能力。通过穿透基质胶包被的滤膜评估的侵袭性,fos-SR-3Y1-202比neo-SR-3Y1-200高约5倍;在fos转移的混合群体细胞系(fos-SR-3Y1-200)和fos转移的高转移性克隆中也观察到了体外高侵袭性。体内肿瘤的组织病理学证据也显示了fos-SR-3Y1-202细胞的高侵袭性。为阐明fos-SR-3Y1-202侵袭性增加的原因,我们检测了细胞与基质胶及其成分(如层粘连蛋白和IV型胶原)的附着、IV型胶原酶活性以及运动性。细胞与培养皿上包被底物的附着或IV型胶原酶的活性没有显著差异。另一方面,使用视频图像分析和计算机技术通过一种直接连续定量细胞形状改变的新方法测定的细胞运动性,fos-SR-3Y1-202比neo-SR-3Y1-200更高。因此,fos转移的细胞系fos-SR-3Y1-202具有高侵袭性,与运动性增强相关,从而导致转移潜能增强。

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