Three-dimensional multicellular cell culture for anti-melanoma drug screening: focus on tumor microenvironment

被引:12
作者
Saleh, Najla Adel [1 ]
Rode, Michele Patricia [1 ]
Sierra, Jelver Alexander [2 ]
Silva, Adny Henrique [3 ]
Miyake, Juliano Andreoli [4 ]
Filippin-Monteiro, Fabiola Branco [5 ]
Creczynski-Pasa, Tania Beatriz [1 ]
机构
[1] Univ Fed Santa Catarina, Dept Ciencias Farmaceut, GEIMM Grp Estudos Interacoes Entre Micro Macromol, S-N Ctr Ciencias,Saude Bloco H-3 Andar, BR-88040900 Florianopolis, SC, Brazil
[2] Univ Fed Santa Catarina, Dept Fis, Florianopolis, SC, Brazil
[3] Univ Fed Santa Catarina, Dept Ciencias Biol, Florianopolis, SC, Brazil
[4] Univ Fed Santa Catarina, Dept Ciencias Morfol, Florianopolis, SC, Brazil
[5] Univ Fed Santa Catarina, Dept Anal Clin, GEIMM Grp Estudos Interacoes Entre Micro Macromol, S-N Ctr Ciencias,Saude Bloco H-3 Andar, BR-88040900 Florianopolis, SC, Brazil
关键词
3D cell culture; Co-culture; Tumor spheroid; Tumor microenvironment; Melanoma; CANCER-ASSOCIATED FIBROBLASTS; MELANOMA-CELLS; STEM-CELLS; MACROPHAGE POLARIZATION; EXTRACELLULAR-MATRIX; TARGETED THERAPY; GROWTH; SPHEROIDS; MODELS; METABOLISM;
D O I
10.1007/s10616-020-00440-5
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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. [GRAPHICS] .
引用
收藏
页码:35 / 48
页数:14
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