Acidic melanoma microenvironment selects for a senescence-like but also migratory-active subpopulation driving metastatic disease

Chiheb C, Fischer S, El Ahmad Z, Henz I, Böhme-Schäfer I, Kappelmann-Fenzl M, Boßerhoff AK (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Cell Death Discovery Nature Publishing Group

Book Volume: 11

Article Number: 469

Journal Issue: 1

DOI: 10.1038/s41420-025-02806-0

Abstract

One of the main characteristics of solid tumors, such as melanoma, is an acidic tumor microenvironment. Due to dysregulation of the cancer cell metabolism and an increased production of acidic metabolites, the tumor acidifies its microenvironment. We hypothesize that this has a strong impact on tumor heterogeneity and the formation of phenotypic subpopulations. Cell culture experiments are usually carried out at a physiological pH of 7.4. Here, we show that long-time acidosis results in the formation of a senescent subpopulation in melanoma cells. Interestingly, after reintroduction to physiological pH, these cells lose their senescence-associated attributes. We isolated this subpopulation using β-galactosidase-dependent C12FDG staining and FACS. Live cell imaging, microscopy, and RNA sequencing analysis revealed that these apparent senescent cells show an increased migratory activity. With this study, we demonstrate that the acidic tumor microenvironment drives tumor plasticity in melanoma and results in the formation of a small subpopulation, which promotes metastasis. (Figure presented.)

Authors with CRIS profile

Chafia Chiheb Lehrstuhl für Biochemie und Molekulare Medizin Ingmar Henz Lehrstuhl für Biochemie und Molekulare Medizin Ines Böhme-Schäfer Lehrstuhl für Biochemie und Molekulare Medizin Melanie Kappelmann-Fenzl Lehrstuhl für Biochemie und Molekulare Medizin Anja Katrin Boßerhoff Lehrstuhl für Biochemie und Molekulare Medizin

Involved external institutions

Technische Hochschule Deggendorf DE Germany (DE)

How to cite

APA:

Chiheb, C., Fischer, S., El Ahmad, Z., Henz, I., Böhme-Schäfer, I., Kappelmann-Fenzl, M., & Boßerhoff, A.K. (2025). Acidic melanoma microenvironment selects for a senescence-like but also migratory-active subpopulation driving metastatic disease. Cell Death Discovery, 11(1). https://doi.org/10.1038/s41420-025-02806-0

MLA:

Chiheb, Chafia, et al. "Acidic melanoma microenvironment selects for a senescence-like but also migratory-active subpopulation driving metastatic disease." Cell Death Discovery 11.1 (2025).

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