[前列腺癌研究进展:3D细胞培养实现肿瘤特征的体外再现]
[Progress in prostate cancer study: 3D cell culture enables the ex vivo reproduction of tumor characteristics].
作者信息
Tostivint Victor, Racaud-Sultan Claire, Roumiguié Mathieu, Soulié Michel, Gamé Xavier, Beauval Jean-Baptiste
机构信息
Hôpital Rangueil, TSA 50032, 1, avenue du professeur Jean-Poulhès, 31059 Toulouse cedex 9, France.
IRSD, université de Toulouse, Inserm, Inra, ENVT, UPS, CS 60039, place du docteur Baylac, 31024 Toulouse cedex 3, France.
出版信息
Presse Med. 2017 Oct;46(10):954-965. doi: 10.1016/j.lpm.2017.06.014. Epub 2017 Sep 28.
Despite new therapeutics options, Prostate Cancer (PCa) remains a public health challenge because of its high incidence and mortality. Limits in PCa research come from the lack of in vitro and in vivo models that mimic the human disease. Currently, 2D in vitro tissue culture models of PCa are widely used but they present numerous limits. They do not reproduce cellular morphology, tissue architecture, inter-patients and intratumor heterogeneity. Furthermore, they lack two key components of PCa tumors, the tumoral microenvironment and the cancer stem cells. In vivo murine models of PCa cannot be representative of all the genetic alterations known in prostate tumors and they hardly reproduce the pathophysiology of human metastatic progression. Consequently, the physiology of these in vitro and in vivo models do not well represent patients tumors. 3D cell cultures overcome many of these limits by sharing morphologic characteristics with in vivo tumors as well as reproducibility of in vitro models. 3D models of PCa include spheroids derived from tumor cell lines, and organoids, derived from patient. In 3D cell cultures, cell fitness is maintained, the physiological cells-cells and cell-matrix interactions are restored and an extracellular matrix surrounds the cells. Organoids, generated from PCa primary tumors or metastases, allow studies on cancer stem cells and their microenvironment. Moreover, organoids retain genetic integrity of PCa tumors. PCa organoid model is an innovative tool that offers great perspectives of therapeutic screening. In the future, organoids generated from patients' biopsies may also lead to personalized medicine.
尽管有了新的治疗选择,但前列腺癌(PCa)因其高发病率和死亡率,仍然是一项公共卫生挑战。PCa研究的局限性源于缺乏能够模拟人类疾病的体外和体内模型。目前,PCa的二维体外组织培养模型被广泛使用,但它们存在诸多局限性。它们无法再现细胞形态、组织结构、患者间和肿瘤内的异质性。此外,它们缺乏PCa肿瘤的两个关键组成部分,即肿瘤微环境和癌症干细胞。PCa的体内小鼠模型不能代表前列腺肿瘤中已知的所有基因改变,并且很难再现人类转移进展的病理生理学。因此,这些体外和体内模型的生理学并不能很好地代表患者的肿瘤。三维细胞培养通过与体内肿瘤共享形态特征以及体外模型的可重复性,克服了许多这些局限性。PCa的三维模型包括源自肿瘤细胞系的球体和源自患者的类器官。在三维细胞培养中,细胞适应性得以维持,生理性的细胞-细胞和细胞-基质相互作用得以恢复,并且细胞周围有细胞外基质。由PCa原发性肿瘤或转移灶生成的类器官允许对癌症干细胞及其微环境进行研究。此外,类器官保留了PCa肿瘤的基因完整性。PCa类器官模型是一种创新工具,为治疗筛选提供了广阔前景。未来,从患者活检组织生成的类器官也可能带来个性化医疗。