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Open AccessArticle

Stroma-Rich Co-Culture Multicellular Tumor Spheroids as a Tool for Photoactive Drugs Screening

1
Centre de Recherche en Automatique de Nancy, Centre National de la Recherche Scientifique UMR 7039, Université de Lorraine, Campus Sciences, Boulevard des Aiguillette, 54506 Vandoeuvre-lès-Nancy, France
2
Research Department, Institut de Cancérologie de Lorraine, 6 avenue de Bourgogne, 54519 Vandoeuvre-lès-Nancy, France
3
Laboratory of Biophysics and Biotechnology, Belarusian State University, 4 Nezavisimosti Avenue, 220030 Minsk, Belarus
4
Institut Jules Bordet, Surgery Department, Université Libre de Bruxelles, Boulevard de Waterloo 121, 1000 Brussel, Belgium
5
Prokhorov General Physics Institute of the Russian Academy of Sciences, Vavilova 38, 117942 Moscow, Russia
6
National Research Nuclear University MEPhI, Kashirskoe shosse, 31, 115409 Moscow, Russia
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(10), 1686; https://doi.org/10.3390/jcm8101686
Received: 16 September 2019 / Revised: 8 October 2019 / Accepted: 11 October 2019 / Published: 15 October 2019
(This article belongs to the Special Issue The Past, Present and Future of Photodynamic Therapy for Cancers)
Conventional 3D multicellular tumor spheroids of head and neck squamous cell carcinoma (HNSCC) consisting exclusively of cancer cells have some limitations. They are compact cell aggregates that do not interact with their extracellular milieu, thus suffering from both insufficient extracellular matrix (ECM) deposition and absence of different types of stromal cells. In order to better mimic in vivo HNSCC tumor microenvironment, we have constructed a 3D stroma-rich in vitro model of HNSCC, using cancer-associated MeWo skin fibroblasts and FaDu pharynx squamous cell carcinoma. The expression of stromal components in heterospheroids was confirmed by immunochemical staining. The generated co-culture FaDu/MeWo spheroids were applied to study penetration, distribution and antitumor efficacy of photoactive drugs such as Temoporfin and Chlorin e6 used in the photodynamic therapy flow cytometry and fluorescence microscopy techniques. We also investigated the distribution of photodiagnostic agent Indocyanine Green. We demonstrated that the presence of stroma influences the behavior of photoactive drugs in different ways: (i) No effect on Indocyanine Green distribution; (ii) lower accumulation of Chlorin e6; (iii) better penetration and PDT efficiency of Temoporfin. Overall, the developed stroma-rich spheroids enlarge the arsenal of in vitro pre-clinical models for high-throughput screening of anti-cancer drugs. View Full-Text
Keywords: photodynamic therapy; temoporfin; head and neck squamous carcinoma; multicellular tumor spheroids; cancer-associated fibroblasts; drug penetration photodynamic therapy; temoporfin; head and neck squamous carcinoma; multicellular tumor spheroids; cancer-associated fibroblasts; drug penetration
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MDPI and ACS Style

Yakavets, I.; Jenard, S.; Francois, A.; Maklygina, Y.; Loschenov, V.; Lassalle, H.-P.; Dolivet, G.; Bezdetnaya, L. Stroma-Rich Co-Culture Multicellular Tumor Spheroids as a Tool for Photoactive Drugs Screening. J. Clin. Med. 2019, 8, 1686. https://doi.org/10.3390/jcm8101686

AMA Style

Yakavets I, Jenard S, Francois A, Maklygina Y, Loschenov V, Lassalle H-P, Dolivet G, Bezdetnaya L. Stroma-Rich Co-Culture Multicellular Tumor Spheroids as a Tool for Photoactive Drugs Screening. Journal of Clinical Medicine. 2019; 8(10):1686. https://doi.org/10.3390/jcm8101686

Chicago/Turabian Style

Yakavets, Ilya; Jenard, Samuel; Francois, Aurelie; Maklygina, Yulia; Loschenov, Victor; Lassalle, Henri-Pierre; Dolivet, Gilles; Bezdetnaya, Lina. 2019. "Stroma-Rich Co-Culture Multicellular Tumor Spheroids as a Tool for Photoactive Drugs Screening" J. Clin. Med. 8, no. 10: 1686. https://doi.org/10.3390/jcm8101686

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