Heralding a new paradigm in 3D tumor modeling.
Heralding a new paradigm in 3D tumor modeling.
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DOI：
10.1016/j.biomaterials.2016.08.052
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发表时间：
2016-11
期刊：
影响因子：
14
通讯作者：
Yu H
中科院分区：
文献类型：
--
作者：
Fong EL;Harrington DA;Farach-Carson MC;Yu H
迄今为止，许多研究已经促成了癌症建模的范式转变，从传统的二维培养系统转移到三维（3D）培养系统用于癌细胞培养。这导致了肿瘤工程的开始，多年来经历了快速的发展。肿瘤不仅仅是大量增殖的癌细胞，而是由动态细胞外基质以及基质细胞、免疫细胞和内皮细胞组成的高度复杂的组织，根据这一认识，已经做出了重大努力来更好地再现3D中的肿瘤微环境。这些方法包括开发工程基质和共培养物，以在体外复制肿瘤-基质相互作用的复杂性。然而，肿瘤工程和癌症生物学领域传统上严重依赖于使用癌细胞系作为肿瘤建模中的细胞来源。虽然癌细胞系为癌症生物学提供了丰富的知识，但这种细胞来源的使用越来越被认为是药物开发中肿瘤药物令人沮丧的失败率的主要因素。支持这一观点的是越来越多的证据表明，肿瘤具有内在的异质性，主要是同质的癌细胞系反映不佳。肿瘤异质性导致患者的治疗耐药性。为了克服这一限制，癌细胞系开始被原发性肿瘤细胞来源所取代，其形式为患者来源的异种移植物和类器官培养物。展望未来，我们提出肿瘤工程的进一步发展将需要将肿瘤异质性（肿瘤变体）与肿瘤复杂性（肿瘤-基质相互作用）一起考虑在内。在这篇综述中，我们提供了一个全面的概述已经取得了什么样的肿瘤的复杂性，并讨论了将肿瘤异质性纳入三维体外肿瘤模型的重要性。这项工作为3D肿瘤工程绘制了路线图，并强调了我们进入下一章时需要解决的一些挑战。
Numerous studies to date have contributed to a paradigm shift in modeling cancer, moving from the traditional two-dimensional culture system to three-dimensional (3D) culture systems for cancer cell culture. This led to the inception of tumor engineering, which has undergone rapid advances over the years. In line with the recognition that tumors are not merely masses of proliferating cancer cells but rather, highly complex tissues consisting of a dynamic extracellular matrix together with stromal, immune and endothelial cells, significant efforts have been made to better recapitulate the tumor microenvironment in 3D. These approaches include the development of engineered matrices and co-cultures to replicate the complexity of tumor-stroma interactions in vitro. However, the tumor engineering and cancer biology fields have traditionally relied heavily on the use of cancer cell lines as a cell source in tumor modeling. While cancer cell lines have contributed to a wealth of knowledge in cancer biology, the use of this cell source is increasingly perceived as a major contributing factor to the dismal failure rate of oncology drugs in drug development. Backing this notion is the increasing evidence that tumors possess intrinsic heterogeneity, which predominantly homogeneous cancer cell lines poorly reflect. Tumor heterogeneity contributes to therapeutic resistance in patients. To overcome this limitation, cancer cell lines are beginning to be replaced by primary tumor cell sources, in the form of patient-derived xenografts and organoids cultures. Moving forward, we propose that further advances in tumor engineering would require that tumor heterogeneity (tumor variants) be taken into consideration together with tumor complexity (tumor-stroma interactions). In this review, we provide a comprehensive overview of what has been achieved in recapitulating tumor complexity, and discuss the importance of incorporating tumor heterogeneity into 3D in vitro tumor models. This work carves out the roadmap for 3D tumor engineering and highlights some of the challenges that need to be addressed as we move forward into the next chapter.
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影响因子：
6.4
作者：
Burdett, Emily;Kasper, F. Kurtis;Ludwig, Joseph A.
通讯作者：
Ludwig, Joseph A.
DOI：
10.1038/nrc2442
发表时间：
2008-08
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.1
作者：
Cassereau, Luke;Miroshnikova, Yekaterina A.;Ou, Guanqing;Lakins, Johnathon;Weaver, Valerie M.
通讯作者：
Weaver, Valerie M.
影响因子：
--
作者：
Arjaans M;Schröder CP;Oosting SF;Dafni U;Kleibeuker JE;de Vries EG
通讯作者：
de Vries EG
影响因子：
9
作者：
Alonso-Nocelo, M.;Abuin, C.;de la Fuente, M.
通讯作者：
de la Fuente, M.