Non-invasive skin sampling of tryptophan/kynurenine ratio in vitro towards a skin cancer biomarker
Jankovskaja, Skaidre LU ; Engblom, Johan ; Rezeli, Melinda LU
; Marko-Varga, György
LU
; Ruzgas, Tautgirdas
LU
and Björklund, Sebastian
LU
(2021)
In Scientific Reports
11(1).
- Abstract
The tryptophan to kynurenine ratio (Trp/Kyn) has been proposed as a cancer biomarker. Non-invasive topical sampling of Trp/Kyn can therefore serve as a promising concept for skin cancer diagnostics. By performing in vitro pig skin permeability studies, we conclude that non-invasive topical sampling of Trp and Kyn is feasible. We explore the influence of different experimental conditions, which are relevant for the clinical in vivo setting, such as pH variations, sampling time, and microbial degradation of Trp and Kyn. The permeabilities of Trp and Kyn are overall similar. However, the permeated Trp/Kyn ratio is generally higher than unity due to endogenous Trp, which should be taken into account to obtain a non-biased Trp/Kyn ratio... (More)
The tryptophan to kynurenine ratio (Trp/Kyn) has been proposed as a cancer biomarker. Non-invasive topical sampling of Trp/Kyn can therefore serve as a promising concept for skin cancer diagnostics. By performing in vitro pig skin permeability studies, we conclude that non-invasive topical sampling of Trp and Kyn is feasible. We explore the influence of different experimental conditions, which are relevant for the clinical in vivo setting, such as pH variations, sampling time, and microbial degradation of Trp and Kyn. The permeabilities of Trp and Kyn are overall similar. However, the permeated Trp/Kyn ratio is generally higher than unity due to endogenous Trp, which should be taken into account to obtain a non-biased Trp/Kyn ratio accurately reflecting systemic concentrations. Additionally, prolonged sampling time is associated with bacterial Trp and Kyn degradation and should be considered in a clinical setting. Finally, the experimental results are supported by the four permeation pathways model, predicting that the hydrophilic Trp and Kyn molecules mainly permeate through lipid defects (i.e., the porous pathway). However, the hydrophobic indole ring of Trp is suggested to result in a small but noticeable relative increase of Trp diffusion via pathways across the SC lipid lamellae, while the shunt pathway is proposed to slightly favor permeation of Kyn relative to Trp.
(Less)
- author
- Jankovskaja, Skaidre
LU
; Engblom, Johan
; Rezeli, Melinda
LU
; Marko-Varga, György
LU
; Ruzgas, Tautgirdas
LU
and Björklund, Sebastian
LU
- organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 11
- issue
- 1
- article number
- 678
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85099386099
- pmid:33436784
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-020-79903-w
- language
- English
- LU publication?
- yes
- id
- 04afa8e7-b1df-43cb-bda0-c9b7b4dfb92e
- date added to LUP
- 2021-01-22 10:42:50
- date last changed
- 2024-12-14 02:18:49
@article{04afa8e7-b1df-43cb-bda0-c9b7b4dfb92e,
abstract = {{<p>The tryptophan to kynurenine ratio (Trp/Kyn) has been proposed as a cancer biomarker. Non-invasive topical sampling of Trp/Kyn can therefore serve as a promising concept for skin cancer diagnostics. By performing in vitro pig skin permeability studies, we conclude that non-invasive topical sampling of Trp and Kyn is feasible. We explore the influence of different experimental conditions, which are relevant for the clinical in vivo setting, such as pH variations, sampling time, and microbial degradation of Trp and Kyn. The permeabilities of Trp and Kyn are overall similar. However, the permeated Trp/Kyn ratio is generally higher than unity due to endogenous Trp, which should be taken into account to obtain a non-biased Trp/Kyn ratio accurately reflecting systemic concentrations. Additionally, prolonged sampling time is associated with bacterial Trp and Kyn degradation and should be considered in a clinical setting. Finally, the experimental results are supported by the four permeation pathways model, predicting that the hydrophilic Trp and Kyn molecules mainly permeate through lipid defects (i.e., the porous pathway). However, the hydrophobic indole ring of Trp is suggested to result in a small but noticeable relative increase of Trp diffusion via pathways across the SC lipid lamellae, while the shunt pathway is proposed to slightly favor permeation of Kyn relative to Trp.</p>}},
author = {{Jankovskaja, Skaidre and Engblom, Johan and Rezeli, Melinda and Marko-Varga, György and Ruzgas, Tautgirdas and Björklund, Sebastian}},
issn = {{2045-2322}},
language = {{eng}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{Non-invasive skin sampling of tryptophan/kynurenine ratio in vitro towards a skin cancer biomarker}},
url = {{http://dx.doi.org/10.1038/s41598-020-79903-w}},
doi = {{10.1038/s41598-020-79903-w}},
volume = {{11}},
year = {{2021}},
}