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TOPICAL SAMPLING OF POTENTIAL SKIN CANCER BIOMARKERS, KYNURENINE AND TRYPTOPHAN: STUDY ON A 3D MELANOMA MODEL
2022 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Background: Malignant melanoma continues to be one of the deadliest forms of skin cancer. Despite immense international efforts, it remains a major clinical challenge. To date, the golden standard for skin cancer diagnosis is through visual inspection and biopsies. UVB (280-320 nm) and IFN-γ have been proven to induce IDO-1 expression in tumor cells, increasing the ratio between tryptophan (Trp) and kynurenine (Kyn) in the tumor microenvironment. Non-invasive sampling of kyn and trp could thereby serve as an alternative for skin cancer diagnostics. 

Objective: This study aimed to investigate the clinical relevance of monitoring trp and kyn by stimulation of skin cancer development in a 3D melanoma model.

Methods: Polystyrene scaffolds were used to create 3D melanoma and melanocyte models respectively. Monolayers were used to examine keratinocytes, fibroblasts, melanoma cells, and melanocytes' response to stimuli. After treatment with UVB and IFN-g, the release of cytokines was measured with ELISA, and gene expression was analyzed with quantitative reverse transcription PCR. Secreted trp and kyn were quantified by high-performance liquid chromatography. The 3D models were then sectioned into 3 µm thick pieces for histological analysis and immunohistochemistry staining.

Results: Significantly increased gene expression of IDO-1 was seen in all monolayers, including the 3D models stimulated with IFN-g. Released IL-6 was induced after UVB exposure in the 3D models, and IL-1a was only detected in the melanocyte model. Both models showed an increase in kyn levels after stimulation with IFN-g. No induced IDO-1 gene expression could be detected in the models after UVB exposure, and no significant change in Trp/Kyn ratio was detected in those samples. 

Conclusion: Our results suggest that IFN-g induces IDO-1 gene expression in 3D models, leading to an increased trp/kyn ratio. Topical sampling of kyn and trp may be possible as an alternative non-invasive method to present diagnostics. UVB seemed to induce inflammation in the 3D models, but no significant signs of malignant transformation.

Place, publisher, year, edition, pages
2022.
Keywords [en]
3D models, IDO-1, Kynurenine, Monolayers, Pro-inflammatory cytokines, Tryptophan.
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:mau:diva-54591OAI: oai:DiVA.org:mau-54591DiVA, id: diva2:1690941
Educational program
HS Biomedical Surface Science
Supervisors
Examiners
Available from: 2022-09-01 Created: 2022-08-28 Last updated: 2022-09-01Bibliographically approved

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Miletic Dahlström, Ruzica
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

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