Three-dimensional multicellular cell culture for anti-melanoma drug screening: focus on tumor microenvironment
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ORIGINAL ARTICLE
Three-dimensional multicellular cell culture for antimelanoma drug screening: focus on tumor microenvironment Najla Adel Saleh . Michele Patrı´cia Rode . Jelver Alexander Sierra . Adny Henrique Silva . Juliano Andreoli Miyake . Fabı´ola Branco Filippin-Monteiro . Taˆnia Beatriz Creczynski-Pasa
Received: 20 July 2020 / Accepted: 4 November 2020 Springer Nature B.V. 2020
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 antiinflammatory 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
N. A. Saleh M. P. Rode T. B. Creczynski-Pasa (&) Departamento de Cieˆncias Farmaceˆuticas, GEIMM— Grupo de Estudos de Interac¸o˜es entre Micro e Macromole´culas, Universidade Federal de Santa Catarina, S/N Centro de Cieˆncias da Sau´de Bloco H - 3 andar, sala H302—Bairro Trindade, Floriano´polis, Santa Catarina CEP: 88040-900, Brazil e-mail: [email protected]
A. H. Silva Departamento de Cieˆncias Biolo´gicas, Universidade Federal de Santa Catarina, Floriano´polis, SC, Brazil e-mail: [email protected]
N. A. Saleh e-mail: [email protected] M. P. Rode e-mail: [email protected] J. A. Sierra Departamento de Fı´sica, Universidade Federal de Santa Catarina, Floriano´polis, SC, Brazil e-mail: [email protected]
J. A. Miyake Departamento de Cieˆncias Morfolo´gicas, Universidade Federal de Santa Catarina, Floriano´polis, SC, Brazil e-mail: [email protected] F. B. Filippin-Monteiro (&) Departamento de Ana´lises Clı´nicas, GEIMM—Grupo de Estudos de Interac¸o˜es entre Micro e Macromole´culas, Universidade Federal de Santa Catarina, S/N Centro de Cieˆncias da Sau´de Bloco H - 3 andar, sala H302—Bairro Trindade, Floriano´polis, Santa Catarina CEP: 88040-900, Brazil e-mail: [email protected]
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Cytotechnology
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 s
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