蛋氨酸依赖性与恶性肿瘤其他特征的关联

Linkage of Methionine Dependence and Other Features of Malignancy.

作者信息

Hoffman Robert M, Erbe Richard W

机构信息

AntiCancer, Inc., San Diego, CA, USA.

Department of Surgery, University of California, San Diego, CA, USA.

出版信息

Methods Mol Biol. 2019;1866:27-36. doi: 10.1007/978-1-4939-8796-2_3.

DOI:10.1007/978-1-4939-8796-2_3

PMID:30725405

Abstract

Cancer cells have an elevated methionine (MET) requirement compared to normal cells and are termed MET dependent. Cancer cells were isolated in MET-restricted (MR) medium that reverted from MET dependence to MET independence. Increased MET biosynthesis was not a prerequisite for reversion to MET independence, indicating that MET dependence was not due to reduced endogenous MET synthesis. MET-independent revertants of cancer cells concomitantly reverted for some of the other properties associated with malignancy: Of the 13 MET-independent revertants isolated 5 showed increased anchorage dependence as reflected by reduced cloning efficiencies in methylcellulose; 8 showed an increased serum requirement for optimal growth; 8 showed decreased cell density in medium containing high serum; and 3 altered their cell morphology significantly. Eight of the 13 revertants have increased chromosome numbers. Thus, by selecting for MET independence, it is possible to obtain heterogeneous reduced-malignancy revertants, indicating further a relationship between altered MET metabolism and other fundamental properties of oncogenic transformation.

摘要

与正常细胞相比，癌细胞对蛋氨酸（MET）的需求增加，被称为MET依赖型。在MET限制（MR）培养基中分离出癌细胞，这些癌细胞从MET依赖型转变为MET非依赖型。MET生物合成增加并非转变为MET非依赖型的先决条件，这表明MET依赖并非由于内源性MET合成减少所致。癌细胞的MET非依赖型回复突变体同时在一些与恶性肿瘤相关的其他特性上也发生了回复突变：在分离出的13个MET非依赖型回复突变体中，5个表现出锚定依赖性增加，这通过甲基纤维素中克隆效率降低得以体现；8个表现出最佳生长所需血清增加；8个在含有高血清的培养基中细胞密度降低；3个细胞形态发生显著改变。13个回复突变体中有8个染色体数目增加。因此，通过选择MET非依赖型，可以获得异质性的恶性程度降低的回复突变体，这进一步表明MET代谢改变与致癌转化的其他基本特性之间存在关联。