A 3D biofabricated cutaneous squamous cell carcinoma tissue model with multi-channel confocal microscopy imaging biomarkers to quantify antitumor effects of chemotherapeutics in tissue.

Autor:	Browning JR; Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA., Derr P; National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, USA., Derr K; National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, USA., Doudican N; The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York, USA., Michael S; National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, USA., Lish SR; Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA., Taylor NA; The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York, USA., Krueger JG; Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA., Ferrer M; National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, USA., Carucci JA; The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York, USA., Gareau DS; Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2020 Jul 07; Vol. 11 (27), pp. 2587-2596. Date of Electronic Publication: 2020 Jul 07 (Print Publication: 2020).
DOI:	10.18632/oncotarget.27570
Abstrakt:	Cutaneous squamous cell carcinoma (cSCC) causes approximately 10,000 deaths annually in the U. S. Current therapies are largely ineffective against metastatic and locally advanced cSCC. There is a need to identify novel, effective, and less toxic small molecule cSCC therapeutics. We developed a 3-dimensional bioprinted skin (3DBPS) model of cSCC tumors together with a microscopy assay to test chemotherapeutic effects in tissue. The full thickness SCC tissue model was validated using hematoxylin and eosin (H&E) and immunohistochemical histological staining, confocal microscopy, and cDNA microarray analysis. A nondestructive, 3D fluorescence confocal imaging assay with tdTomato-labeled A431 SCC and ZsGreen-labeled keratinocytes was developed to test efficacy and general toxicity of chemotherapeutics. Fluorescence-derived imaging biomarkers indicated that 50% of cancer cells were killed in the tissue after 1μM 5-Fluorouracil 48-hour treatment, compared to a baseline of 12% for untreated controls. The imaging biomarkers also showed that normal keratinocytes were less affected by treatment (11% killed) than the untreated tissue, which had no significant killing effect. Data showed that 5-Fluorouracil selectively killed cSCC cells more than keratinocytes. Our 3DBPS assay platform provides cellular-level measurement of cell viability and can be adapted to achieve nondestructive high-throughput screening (HTS) in bio-fabricated tissues. Competing Interests: CONFLICTS OF INTEREST The authors state no conflicts of interest. (Copyright: © 2020 Browning et al.)
Databáze:	MEDLINE
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