Extracellular control of chromosomal instability and maintenance of intra-tumoral heterogeneity
作者机构：UC Irvine Brain Tumor Laboratory in Department of SurgeryUniversity of CaliforniaIrvineIrvineCA 92697USA
出 版 物：《Journal of Cancer Metastasis and Treatment》 (癌症转移与治疗（英文版）)
年 卷 期：2018年第4卷第1期
页 面：468-482页
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
主 题：Malignant glioma intra-tumoral heterogeneity functional tumor subpopulations chromosome 7 chromosome
摘 要：Aim:Current cancer treatments are challenged by the plasticity of cancer cells,largely influenced by chromosomal instability(CIN)leading to variations in karyotype known as tumor-specific aneuploidy,which in turn,leads to intra-tumor cellular heterogeneity(TH).Cells with certain chromosomal defects often survive treatment and the growth-associated states of TH persist in recurrent *** of the CIN rate seems to reside within the tumor *** an attempt to develop a therapy targeting cancer plasticity,we studied the possible extracellular control of CIN rate in Chr7-defined TH in ***:Chr7-fluorescence in situ hybridization was applied on various grades of gliomas,in vitro cultures and intracranial xenografts of two syngeneic glioma lines(U251 and U251-NS)derived from various cell-inoculating densities,with or without EFEMP1 ***:A grade-dependent increase of trisomy-7 population and Chr7-defined cell diversity was shown in gliomas.A negative association between Chr7-MS rate and initial cell-inoculating density was observed which was prevented by EFEMP1 ***:Our data demonstrate that CIN is a major driver for cancer cell plasticity and suggest that CIN can be controlled by extracellular factors derived from normal and tumor cells,and EFEMP1 is one of these factors.
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