Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Michael Smith Genome Sciences Center, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Laboratoire d'Oncobiologie, Hôpital René Huguenin, Institut Curie, St Cloud, France; Université Paris Descartes, Faculté de Pharmacie de Paris, Sorbonne Paris Cité, Paris, France.
Laboratoire d'Oncobiologie, Hôpital René Huguenin, Institut Curie, St Cloud, France; Université Paris Descartes, Faculté des Sciences Pharmaceutiques et Biologiques, UMR 8151 CNRS-U1022 Inserm, Sorbonne Paris Cité, Paris, France.
Neoplasia. 2015 Jan;17(1):1-15. doi: 10.1016/j.neo.2014.12.004.
Three-dimensional (3D) in vitro models have been used in cancer research as an intermediate model between in vitro cancer cell line cultures and in vivo tumor. Spherical cancer models represent major 3D in vitro models that have been described over the past 4 decades. These models have gained popularity in cancer stem cell research using tumorospheres. Thus, it is crucial to define and clarify the different spherical cancer models thus far described. Here, we focus on in vitro multicellular spheres used in cancer research. All these spherelike structures are characterized by their well-rounded shape, the presence of cancer cells, and their capacity to be maintained as free-floating cultures. We propose a rational classification of the four most commonly used spherical cancer models in cancer research based on culture methods for obtaining them and on subsequent differences in sphere biology: the multicellular tumor spheroid model, first described in the early 70s and obtained by culture of cancer cell lines under nonadherent conditions; tumorospheres, a model of cancer stem cell expansion established in a serum-free medium supplemented with growth factors; tissue-derived tumor spheres and organotypic multicellular spheroids, obtained by tumor tissue mechanical dissociation and cutting. In addition, we describe their applications to and interest in cancer research; in particular, we describe their contribution to chemoresistance, radioresistance, tumorigenicity, and invasion and migration studies. Although these models share a common 3D conformation, each displays its own intrinsic properties. Therefore, the most relevant spherical cancer model must be carefully selected, as a function of the study aim and cancer type.
三维（3D）体外模型已被用于癌症研究，作为体外癌细胞系培养与体内肿瘤之间的中间模型。球形癌症模型是过去 40 年来描述的主要 3D 体外模型之一。这些模型在肿瘤球体的癌症干细胞研究中得到了广泛应用。因此，定义和澄清迄今为止描述的不同球形癌症模型非常重要。在这里，我们专注于癌症研究中使用的体外多细胞球体。所有这些类似球体的结构都具有圆润的形状、癌细胞的存在以及作为游离培养物维持的能力的特征。我们根据获得它们的培养方法以及随后球体生物学的差异，对癌症研究中最常用的四种球形癌症模型进行了合理分类：多细胞肿瘤球体模型，最早于 70 年代初描述，并通过在非附着条件下培养癌细胞系获得；肿瘤球体，一种在无血清培养基中添加生长因子建立的癌症干细胞扩增模型；组织来源的肿瘤球体和器官样多细胞球体，通过肿瘤组织的机械解离和切割获得。此外，我们描述了它们在癌症研究中的应用和兴趣；特别是，我们描述了它们在化疗耐药性、放射抗性、致瘤性以及侵袭和迁移研究中的贡献。尽管这些模型具有共同的 3D 构象，但每个模型都显示出其自身的固有特性。因此，必须根据研究目的和癌症类型仔细选择最相关的球形癌症模型。
