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UM-Chor1:首个经验证的颅底脊索瘤细胞系的建立与特性鉴定。

UM-Chor1: establishment and characterization of the first validated clival chordoma cell line.

机构信息

Departments of1Otolaryngology-Head and Neck Surgery.

2Neurosurgery, and.

出版信息

J Neurosurg. 2018 Mar;128(3):701-709. doi: 10.3171/2016.10.JNS16877. Epub 2017 Apr 21.

Abstract

OBJECTIVE Chordomas are rare malignant tumors thought to arise from remnants of the notochord. They can be located anywhere along the axial skeleton but are most commonly found in the clival and sacrococcygeal regions, where the notochord regresses during fetal development. Chordomas are resistant to many current therapies, leaving surgery as the primary method of treatment. Cancer cell lines have been useful for developing new cancer treatments in a laboratory setting that can then be transferred to the clinic, but there are only 4 validated chordoma cell lines available. The objective of this work was to establish chordoma cell lines from surgical tissue in order to expand the library of lines available for laboratory research. METHODS Chordoma tissue from the clivus was processed and sorted by flow cytometry to obtain an isolated population of chordoma cells. These cells were grown in culture and expanded until enough doublings to consider the line established. Identification of a chordoma cell line was made with known markers for chordoma, and the line was observed for ALDH (aldehyde dehydrogenase) subpopulations and tested in serum-free growth conditions as well as in vivo. RESULTS A fifth chordoma cell line, UM-Chor1, was successfully established. This is the first chordoma cell line originating from the clivus. Validation was confirmed by phenotype and positivity for the chordoma markers CD24 and brachyury. The authors also attempted to identify an ALDH cell population in UM-Chor1, UCH1, and UCH2 but did not detect a distinct population. UM-Chor1 cells were able to form spheroids in serum-free culture, were successfully transduced with luciferase, and could be injected parasacrally and grown in NOD/SCID mice. CONCLUSIONS The availability of this novel clival chordoma cell line for in vitro and in vivo research provides an opportunity for developments in treatment against the disease.

摘要

目的

脊索瘤是一种罕见的恶性肿瘤,被认为起源于脊索的残留物。它们可以位于沿轴骨骼的任何部位,但最常见于颅底和尾骨区域,在胎儿发育过程中脊索退化。脊索瘤对许多当前的治疗方法具有抗性,因此手术成为主要的治疗方法。癌细胞系在实验室环境中开发新的癌症治疗方法非常有用,然后可以将这些方法转移到临床,但是目前只有 4 种经过验证的脊索瘤细胞系可用。这项工作的目的是从手术组织中建立脊索瘤细胞系,以扩大可用于实验室研究的细胞系库。

方法

通过流式细胞术对颅底的脊索瘤组织进行处理和分选,以获得分离的脊索瘤细胞群。将这些细胞在培养中生长并扩增,直到达到足以考虑建立细胞系的倍增数。使用已知的脊索瘤标志物鉴定脊索瘤细胞系,并观察该系的 ALDH(醛脱氢酶)亚群,以及在无血清生长条件下和体内进行测试。

结果

成功建立了第五种脊索瘤细胞系 UM-Chor1。这是第一个源自颅底的脊索瘤细胞系。通过表型和脊索瘤标志物 CD24 和 brachyury 的阳性验证了该系的建立。作者还试图在 UM-Chor1、UCH1 和 UCH2 中鉴定 ALDH 细胞群,但未检测到明显的群体。UM-Chor1 细胞能够在无血清培养中形成球体,可成功转导荧光素酶,并可注射到尾旁并在 NOD/SCID 小鼠中生长。

结论

这种新型颅底脊索瘤细胞系的可用性为疾病的治疗提供了体外和体内研究的机会。

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