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

Oncotarget
James R BrowningDaniel S Gareau

Abstract

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 mo...Continue Reading

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Citations

Jan 26, 2021·Translational Oncology·Robin AugustineAnwarul Hasan
Sep 4, 2021·Materials Science & Engineering. C, Materials for Biological Applications·Helena Herrada-ManchónMaría-Dolores Chiara

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Methods Mentioned

BETA
confocal microscopy
fluorescence microscopy
fluorescence imaging
RNA-Seq
biopsies
biopsy

Software Mentioned

Basepair
Measure of Effect Size Toolbox
DEseq
MATLAB

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