Immunhistochemische Analyse einer Hypoxie-assoziierten Signatur in Melanomen mit positivem und negativem Schildwächterlymphknoten

Der Hautarzt ◽

10.1007/s00105-021-04934-x ◽

2022 ◽

Author(s):

Ferdinand Toberer ◽

Julia K. Winkler ◽

Holger A. Haenssle ◽

Monika Heinzel-Gutenbrunner ◽

Alexander Enk ◽

...

Keyword(s):

Ph Regulation ◽

Hypoxia Inducible Factors ◽

Glut 1

ZusammenfassungMetabolische Anpassungsprozesse, vermittelt durch sog. Hypoxie-induzierbare Faktoren und deren Zielgene, spielen in zahlreichen Malignomen eine wichtige Rolle. Rasch wachsende Tumoren können ihre Stoffwechselvorgänge an eine auftretende Hypoxie anpassen. So werden beispielsweise nach der Aktivierung des „Hypoxia inducible-factors-1α“ Modifikationen am Glukosestoffwechsel, der intrazellulären pH-Regulation oder der Angiogenese initiiert. In dieser immunhistochemischen Pilotstudie analysierten wir primär kutane Melanome mit positivem und negativem Schildwächterlymphknotenstatus im Hinblick auf mögliche Unterschiede ihrer metabolischen Signatur. Hierbei konnten wir unter anderem zeigen, dass die Expression von Glukosetransporter‑1 (GLUT-1) sowohl in allen Melanomen ohne Subgruppenanalyse, als auch in der Subgruppe mit negativem Schildwächterlymphknoten positiv mit der Tumordicke sowie dem Vorliegen einer Ulzeration korrelierte. Zudem korrelierte bei Melanomen mit positivem Schildwächterlymphknoten die Expression von vaskulärem endothelialem Wachstumsfaktor (VEGF) positiv mit dem Vorliegen einer Ulzeration.

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The genotypic and phenotypic impact of hypoxia microenvironment on glioblastoma cell lines

BMC Cancer ◽

10.1186/s12885-021-08978-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Lucy Wanjiku Macharia ◽

Wanjiru Muriithi ◽

Carlos Pilotto Heming ◽

Dennis Kirii Nyaga ◽

Veronica Aran ◽

...

Keyword(s):

Cell Lines ◽

Patient Survival ◽

Morphological Changes ◽

Tumour Microenvironment ◽

Cell Phenotype ◽

Hypoxia Inducible Factors ◽

Glut 1 ◽

Adaptation Mechanisms ◽

Poor Patient ◽

Poor Patient Survival

Abstract Background Glioblastoma is a fatal brain tumour with a poor patient survival outcome. Hypoxia has been shown to reprogram cells towards a stem cell phenotype associated with self-renewal and drug resistance properties. Activation of hypoxia-inducible factors (HIFs) helps in cellular adaptation mechanisms under hypoxia. Similarly, miRNAs are known to be dysregulated in GBM have been shown to act as critical mediators of the hypoxic response and to regulate key processes involved in tumorigenesis. Methods Glioblastoma (GBM) cells were exposed to oxygen deprivation to mimic a tumour microenvironment and different cell aspects were analysed such as morphological changes and gene expression of miRNAs and survival genes known to be associated with tumorigenesis. Results It was observed that miR-128a-3p, miR-34-5p, miR-181a/b/c, were down-regulated in 6 GBM cell lines while miR-17-5p and miR-221-3p were upregulated when compared to a non-GBM control. When the same GBM cell lines were cultured under hypoxic microenvironment, a further 4–10-fold downregulation was observed for miR-34-5p, miR-128a-3p and 181a/b/c while a 3–6-fold upregulation was observed for miR-221-3p and 17-5p for most of the cells. Furthermore, there was an increased expression of SOX2 and Oct4, GLUT-1, VEGF, Bcl-2 and survivin, which are associated with a stem-like state, increased metabolism, altered angiogenesis and apoptotic escape, respectively. Conclusion This study shows that by mimicking a tumour microenvironment, miRNAs are dysregulated, stemness factors are induced and alteration of the survival genes necessary for the cells to adapt to the micro-environmental factors occurs. Collectively, these results might contribute to GBM aggressiveness.

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