College of Pharmacy, Roosevelt University, Chicago, IL, USA.
Department of Obstetrics and Gynecology, Gordon Center of Integrative Sciences, W116, University of Chicago, Chicago, IL, USA.
Adv Exp Med Biol. 2021;1330:75-94. doi: 10.1007/978-3-030-73359-9_5.
The majority of ovarian cancer patients present clinically with wide-spread metastases throughout the peritoneal cavity, metastasizing to the mesothelium-lined peritoneum and visceral adipose depots within the abdomen. This unique metastatic tumor microenvironment is comprised of multiple cell types, including mesothelial cells, fibroblasts, adipocytes, macrophages, neutrophils, and T lymphocytes. Modeling advancements, including complex 3D systems and organoids, coupled with 2D cocultures, in vivo mouse models, and ex vivo human tissue cultures have greatly enhanced our understanding of the tumor-stroma interactions that are required for successful metastasis of ovarian cancer cells. However, advanced multifaceted model systems that incorporate frequency and spatial distribution of all cell types present in the tumor microenvironment of ovarian cancer are needed to enhance our knowledge of ovarian cancer biology in order to identify methods for preventing and treating metastatic disease. This review highlights the utility of recently developed modeling approaches, summarizes some of the resulting progress using these techniques, and suggests how these strategies may be implemented to elucidate signaling processes among cell types of the tumor microenvironment that promote ovarian cancer metastasis.
大多数卵巢癌患者在临床上表现为广泛的腹膜腔转移，转移到腹膜间皮和腹部内脏脂肪库。这种独特的转移性肿瘤微环境由多种细胞类型组成，包括间皮细胞、成纤维细胞、脂肪细胞、巨噬细胞、中性粒细胞和 T 淋巴细胞。建模进展，包括复杂的 3D 系统和类器官，以及 2D 共培养物、体内小鼠模型和体外人组织培养，极大地提高了我们对卵巢癌细胞成功转移所需的肿瘤-基质相互作用的理解。然而，需要先进的多方面模型系统，将卵巢癌肿瘤微环境中存在的所有细胞类型的频率和空间分布纳入其中，以增强我们对卵巢癌生物学的认识，从而确定预防和治疗转移性疾病的方法。本综述强调了最近开发的建模方法的实用性，总结了使用这些技术取得的一些进展，并提出了如何实施这些策略以阐明促进卵巢癌转移的肿瘤微环境中细胞类型之间的信号转导过程。
