Cytotechnology ( IF 2.0 ) Pub Date : 2020-11-20 , DOI: 10.1007/s10616-020-00440-5 Najla Adel Saleh 1 , Michele Patrícia Rode 1 , Jelver Alexander Sierra 2 , Adny Henrique Silva 3 , Juliano Andreoli Miyake 4 , Fabíola Branco Filippin-Monteiro 5 , Tânia Beatriz Creczynski-Pasa 1
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Abstract
The development of new treatments for malignant melanoma, which has the worst prognosis among skin neoplasms, remains a challenge. The tumor microenvironment aids tumor cells to grow and resist to chemotherapeutic treatment. One way to mimic and study the tumor microenvironment is by using three-dimensional (3D) co-culture models (spheroids). In this study, a melanoma heterospheroid model composed of cancer cells, fibroblasts, and macrophages was produced by liquid-overlay technique using the agarose gel. The size, growth, viability, morphology, cancer stem-like cells population and inflammatory profile of tumor heterospheroids and monospheroids were analyzed to evaluate the influence of stromal cells on these parameters. Furthermore, dacarbazine cytotoxicity was evaluated using spheroids and two-dimensional (2D) melanoma model. After finishing the experiments, it was observed the M2 macrophages induced an anti-inflammatory microenvironment in heterospheroids; fibroblasts cells support the formation of the extracellular matrix, and a higher percentage of melanoma CD271 was observed in this model. Additionally, melanoma spheroids responded differently to the dacarbazine than the 2D melanoma culture as a result of their cellular heterogeneity and 3D structure. The 3D model was shown to be a fast and reliable tool for drug screening, which can mimic the in vivo tumor microenvironment regarding interactions and complexity.
Graphic abstract
中文翻译：
用于抗黑色素瘤药物筛选的三维多细胞细胞培养：关注肿瘤微环境
摘要
在皮肤肿瘤中预后最差的恶性黑色素瘤的新疗法的开发仍然是一个挑战。肿瘤微环境有助于肿瘤细胞生长并抵抗化疗。模拟和研究肿瘤微环境的一种方法是使用三维 (3D) 共培养模型（球体）。在这项研究中，使用琼脂糖凝胶通过液体覆盖技术制备了由癌细胞、成纤维细胞和巨噬细胞组成的黑色素瘤异球体模型。分析了肿瘤异球体和单球体的大小、生长、活力、形态、癌症干细胞样细胞群和炎症特征，以评估基质细胞对这些参数的影响。此外，使用球体和二维 (2D) 黑色素瘤模型评估了达卡巴嗪的细胞毒性。实验结束后，观察到M2巨噬细胞在异球体中诱导了抗炎微环境；成纤维细胞支持细胞外基质的形成，并且在该模型中观察到较高百分比的黑色素瘤 CD271。此外，由于其细胞异质性和 3D 结构，黑色素瘤球体对达卡巴嗪的反应不同于 2D 黑色素瘤培养物。3D 模型被证明是一种快速可靠的药物筛选工具，可以模拟体内肿瘤微环境的相互作用和复杂性。此外，由于其细胞异质性和 3D 结构，黑色素瘤球体对达卡巴嗪的反应不同于 2D 黑色素瘤培养物。3D 模型被证明是一种快速可靠的药物筛选工具，可以模拟体内肿瘤微环境的相互作用和复杂性。此外，由于其细胞异质性和 3D 结构，黑色素瘤球体对达卡巴嗪的反应不同于 2D 黑色素瘤培养物。3D 模型被证明是一种快速可靠的药物筛选工具，可以模拟体内肿瘤微环境的相互作用和复杂性。
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