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Article Open Access

Metastatic renal cell carcinoma cells growing in 3D on poly‑D‑lysine or laminin present a stem‑like phenotype and drug resistance

  • Authors:
    • Klaudia K. Brodaczewska
    • Zofia F. Bielecka
    • Kamila Maliszewska‑Olejniczak
    • Cezary Szczylik
    • Camillo Porta
    • Ewa Bartnik
    • Anna M. Czarnecka
  • View Affiliations / Copyright

    Affiliations: Department of Oncology with Laboratory of Molecular Oncology, Military Institute of Medicine, 04‑141 Warsaw, Poland, Department of Internal Medicine and Therapeutics, University of Pavia, I‑27100 Pavia, Italy, Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Poland
    Copyright: © Brodaczewska et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1878-1892
    |
    Published online on: September 18, 2019
       https://doi.org/10.3892/or.2019.7321
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Abstract

3D spheroids are built by heterogeneous cell types in different proliferative and metabolic states and are enriched in cancer stem cells. The main aim of the study was to investigate the usefulness of a novel metastatic renal cell carcinoma (RCC) 3D spheroid culture for in vitro cancer stem cell physiology research and drug toxicity screening. RCC cell lines, Caki‑1 (skin metastasis derived) and ACHN (pleural effusion derived), were efficiently cultured in growth‑factor/serum deprived, defined, StemXvivo and Nutristem medium on laminin‑coated or poly‑D‑lysine‑coated plates. In optimal 3D culture conditions, ACHN cells (StemXVivo/poly‑D‑lysine) formed small spheroids with remaining adherent cells of an epithelial phenotype, while Caki‑1 cells (StemXVivo/laminin) formed large dark spheroids with significantly reduced cell viability in the center. In the 3D structures, expression levels of genes encoding stem transcription factors (OCT4, SOX2, NES) and RCC stem cell markers (CD105, CD133) were deregulated in comparison to these expression levels in traditional 2D culture. Sunitinib, epirubicin and doxycycline were more toxic to cells cultured in monolayers than for cells in 3D spheroids. High numbers of cells arrested in the G0/G1 phase of the cell cycle were found in spheroids under sunitinib treatment. We showed that metastatic RCC 3D spheroids supported with ECM are a useful model to determine the cancer cell growth characteristics that are not found in adherent 2D cultures. Due to the more complex architecture, spheroids may mimic in vivo micrometastases and may be more appropriate to investigate novel drug candidate responses, including the direct effects of tyrosine kinase inhibitor activity against RCC cells.
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Copy and paste a formatted citation
Spandidos Publications style
Brodaczewska KK, Bielecka ZF, Maliszewska‑Olejniczak K, Szczylik C, Porta C, Bartnik E and Czarnecka AM: Metastatic renal cell carcinoma cells growing in 3D on poly‑D‑lysine or laminin present a stem‑like phenotype and drug resistance. Oncol Rep 42: 1878-1892, 2019.
APA
Brodaczewska, K.K., Bielecka, Z.F., Maliszewska‑Olejniczak, K., Szczylik, C., Porta, C., Bartnik, E., & Czarnecka, A.M. (2019). Metastatic renal cell carcinoma cells growing in 3D on poly‑D‑lysine or laminin present a stem‑like phenotype and drug resistance. Oncology Reports, 42, 1878-1892. https://doi.org/10.3892/or.2019.7321
MLA
Brodaczewska, K. K., Bielecka, Z. F., Maliszewska‑Olejniczak, K., Szczylik, C., Porta, C., Bartnik, E., Czarnecka, A. M."Metastatic renal cell carcinoma cells growing in 3D on poly‑D‑lysine or laminin present a stem‑like phenotype and drug resistance". Oncology Reports 42.5 (2019): 1878-1892.
Chicago
Brodaczewska, K. K., Bielecka, Z. F., Maliszewska‑Olejniczak, K., Szczylik, C., Porta, C., Bartnik, E., Czarnecka, A. M."Metastatic renal cell carcinoma cells growing in 3D on poly‑D‑lysine or laminin present a stem‑like phenotype and drug resistance". Oncology Reports 42, no. 5 (2019): 1878-1892. https://doi.org/10.3892/or.2019.7321
Copy and paste a formatted citation
x
Spandidos Publications style
Brodaczewska KK, Bielecka ZF, Maliszewska‑Olejniczak K, Szczylik C, Porta C, Bartnik E and Czarnecka AM: Metastatic renal cell carcinoma cells growing in 3D on poly‑D‑lysine or laminin present a stem‑like phenotype and drug resistance. Oncol Rep 42: 1878-1892, 2019.
APA
Brodaczewska, K.K., Bielecka, Z.F., Maliszewska‑Olejniczak, K., Szczylik, C., Porta, C., Bartnik, E., & Czarnecka, A.M. (2019). Metastatic renal cell carcinoma cells growing in 3D on poly‑D‑lysine or laminin present a stem‑like phenotype and drug resistance. Oncology Reports, 42, 1878-1892. https://doi.org/10.3892/or.2019.7321
MLA
Brodaczewska, K. K., Bielecka, Z. F., Maliszewska‑Olejniczak, K., Szczylik, C., Porta, C., Bartnik, E., Czarnecka, A. M."Metastatic renal cell carcinoma cells growing in 3D on poly‑D‑lysine or laminin present a stem‑like phenotype and drug resistance". Oncology Reports 42.5 (2019): 1878-1892.
Chicago
Brodaczewska, K. K., Bielecka, Z. F., Maliszewska‑Olejniczak, K., Szczylik, C., Porta, C., Bartnik, E., Czarnecka, A. M."Metastatic renal cell carcinoma cells growing in 3D on poly‑D‑lysine or laminin present a stem‑like phenotype and drug resistance". Oncology Reports 42, no. 5 (2019): 1878-1892. https://doi.org/10.3892/or.2019.7321
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