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改变表面糖蛋白组成对小鼠乳腺肿瘤细胞转移定植潜能的影响。

Effects of altering surface glycoprotein composition on metastatic colonisation potential of murine mammary tumour cells.

作者信息

Sargent N S, Price J E, Darling D L, Flynn M P, Tarin D

出版信息

Br J Cancer. 1987 Jan;55(1):21-8. doi: 10.1038/bjc.1987.5.

Abstract

This study has examined cells from naturally-occurring murine mammary tumours to ascertain whether cell surface glycoproteins play a significant role in colonisation of the lungs after intravenous inoculation. It was found that gel electrophoretic analysis of membrane extracts and lectin adsorption studies did not reveal any consistent differences in glycoprotein composition of cells from tumours which can heavily colonise the lungs relative to ones from tumours which cannot do so or to cells from pulmonary metastases. Also, alteration of structural and functional properties of surface glycoproteins by treatment with succinylated lectins or with drugs such as tunicamycin and swainsonine, which inhibit glycosylation of membrane proteins, had no specific effects on metastatic colonisation of the lungs. Tunicamycin apparently decreased capability to form experimental metastases but also diminished tumourigenicity on subcutaneous inoculation, although it did not affect tumour cell viability in vitro. This information supports earlier studies from this laboratory involving enzymic digestion of the surface of living tumour cells before inoculation and demonstrates that the pulmonary colonisation capability of these mammary tumour cells can withstand global disorganisation of membrane glycoprotein structure and composition. This implies that either the surface glycoproteins are not important in the colonisation process, or that these tumour cells have great capability for rapid repair of their surfaces. It is concluded that a clear answer to whether surface glycoprotein composition has a decisive role in pulmonary colonisation by these mammary tumour cells requires introduction of stable heritable traits into tumour cell populations by genetic manipulation.

摘要

本研究检测了自然发生的小鼠乳腺肿瘤细胞,以确定细胞表面糖蛋白在静脉接种后肺部定植过程中是否发挥重要作用。研究发现,对膜提取物进行凝胶电泳分析以及凝集素吸附研究表明,与不能大量定植肺部的肿瘤细胞或肺转移瘤细胞相比,能大量定植肺部的肿瘤细胞的糖蛋白组成并无任何一致的差异。此外,用琥珀酰化凝集素或诸如衣霉素和苦马豆素等抑制膜蛋白糖基化的药物处理,改变表面糖蛋白的结构和功能特性,对肺部的转移定植并无特定影响。衣霉素明显降低了形成实验性转移瘤的能力,但也降低了皮下接种时的致瘤性,尽管它并不影响体外肿瘤细胞的活力。这一信息支持了本实验室早期涉及接种前对活肿瘤细胞表面进行酶消化的研究,并表明这些乳腺肿瘤细胞的肺部定植能力能够承受膜糖蛋白结构和组成的整体紊乱。这意味着要么表面糖蛋白在定植过程中并不重要,要么这些肿瘤细胞具有很强的表面快速修复能力。得出的结论是,要明确表面糖蛋白组成在这些乳腺肿瘤细胞肺部定植中是否起决定性作用,需要通过基因操作将稳定的可遗传性状引入肿瘤细胞群体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e61d/2001558/14bf9d8d3321/brjcancer00512-0023-a.jpg

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