Department of Bioengineering, Rice University, Houston, Texas.
Division of Cancer Medicine, Department of Sarcoma Medical Oncology, MD Anderson Cancer Center, The University of Texas, Houston, Texas.
Tissue Eng Part B Rev. 2020 Jun;26(3):249-271. doi: 10.1089/ten.teb.2019.0302. Epub 2020 Feb 14.
Investigations of cancer biology and screening of potential therapeutics for efficacy and safety begin in the preclinical laboratory setting. A staple of most basic research in cancer involves the use of tissue culture plates, on which immortalized cell lines are grown in monolayers. However, this practice has been in use for over six decades and does not account for vital elements of the tumor microenvironment that are thought to aid in initiation, propagation, and ultimately, metastasis of cancer. Furthermore, information gleaned from these techniques does not always translate to animal models or, more crucially, clinical trials in cancer patients. Osteosarcoma (OS) and Ewing sarcoma (ES) are the most common primary tumors of bone, but outcomes for patients with metastatic or recurrent disease have stagnated in recent decades. The unique elements of the bone tumor microenvironment have been shown to play critical roles in the pathogenesis of these tumors and thus should be incorporated in the preclinical models of these diseases. In recent years, the field of tissue engineering has leveraged techniques used in designing scaffolds for regenerative medicine to engineer preclinical tumor models that incorporate spatiotemporal control of physical and biological elements. We herein review the clinical aspects of OS and ES, critical elements present in the sarcoma microenvironment, and engineering approaches to model the bone tumor microenvironment. Impact statement The current paradigm of cancer biology investigation and therapeutic testing relies heavily on monolayer, monoculture methods developed over half a century ago. However, these methods often lack essential hallmarks of the cancer microenvironment that contribute to tumor pathogenesis. Tissue engineers incorporate scaffolds, mechanical forces, cells, and bioactive signals into biological environments to drive cell phenotype. Investigators of bone sarcomas, aggressive tumors that often rob patients of decades of life, have begun to use tissue engineering techniques to devise models for these diseases. Their efforts highlight how critical elements of the cancer microenvironment directly affect tumor signaling and pathogenesis.
癌症生物学的研究和潜在治疗药物的筛选都是从临床前实验室开始的。大多数癌症基础研究的一个主要内容是使用组织培养板，在培养板上单层培养永生化细胞系。然而，这种做法已经使用了六十多年，并没有考虑到肿瘤微环境的重要因素，而这些因素被认为有助于癌症的起始、传播，最终是转移。此外，从这些技术中获得的信息并不总是转化为动物模型，更关键的是，转化为癌症患者的临床试验。骨肉瘤（OS）和尤文肉瘤（ES）是最常见的骨原发性肿瘤，但近几十年来，转移性或复发性疾病患者的预后仍停滞不前。骨肿瘤微环境的独特元素已被证明在这些肿瘤的发病机制中起着关键作用，因此应将其纳入这些疾病的临床前模型中。近年来，组织工程领域利用再生医学中设计支架的技术，构建了包含物理和生物元素时空控制的临床前肿瘤模型。本文综述了 OS 和 ES 的临床方面、肉瘤微环境中的关键因素，以及模拟骨肿瘤微环境的工程方法。
影响说明 目前的癌症生物学研究和治疗测试范式严重依赖于半个多世纪前开发的单层、单培养方法。然而，这些方法往往缺乏促进肿瘤发病机制的癌症微环境的基本特征。组织工程师将支架、机械力、细胞和生物活性信号纳入生物环境中，以驱动细胞表型。骨肉瘤的研究人员，即那些经常剥夺患者数十年生命的侵袭性肿瘤的研究人员，已经开始使用组织工程技术来设计这些疾病的模型。他们的努力强调了癌症微环境的关键因素如何直接影响肿瘤信号和发病机制。
