GPR4 in the pH-dependent migration of melanoma cells in the tumor microenvironment

Stolwijk, Judith Anthea and Wallner, Susanne and Heider, Judith and Kurz, Bernadett and Putz, Lisa and Michaelis, Stefanie and Goricnik, Barbara and Erl, Julia and Frank, Linda and Berneburg, Mark and Haubner, Frank and Wegener, Joachim and Schreml, Stephan (2023) GPR4 in the pH-dependent migration of melanoma cells in the tumor microenvironment. EXPERIMENTAL DERMATOLOGY, 32 (4). pp. 479-490. ISSN 0906-6705, 1600-0625

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Abstract

Due to its high metastatic potential, malignant melanoma is one of the deadliest skin cancers. In melanoma as well as in other cancers, acidification of the tumor microenvironment (=TME, inverse pH-gradient) is a well-known driver of tumor progression and metastasis. Membrane-bound receptors, such as the proton-sensitive GPCR (pH-GPCR) GPR4, are considered as potential initiators of the signalling cascades relevant to malignant transformation. In this study, we investigated the pH-dependent migration of GPR4 wildtype/overexpressing SK-Mel-28 cells using an impedance-based electrical wounding and migration assay and classical Boyden chamber experiments. Migration of GPR4 overexpressing SK-Mel-28 cells was enhanced in a range of pH 6.5-7.5 as compared to controls in the impedance-based electrical wounding and migration assay. In Boyden chamber experiments, GPR4 overexpression only increased migration at pH 7.5 in a Matrigel-free setup, but not at pH 6.5. Results indicate that GPR4 is involved in the migration of melanoma cells, especially in the tumor periphery, and that this process is affected by pH in the TME.

Item Type: Article
Uncontrolled Keywords: PROTEIN-COUPLED RECEPTORS; TDAG8; PROLIFERATION; INVOLVEMENT; METASTASIS; INHIBITION; ADHESION; G2A; Boyden chamber; ECIS; GPR4; impedance; malignant melanoma; migration; pH-GPCR
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Dermatologie und Venerologie
Chemistry and Pharmacy > Institut für Analytische Chemie, Chemo- und Biosensorik > Chemo- und Biosensorik (Prof. Antje J. Bäumner, formerly Prof. Wolfbeis)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 09 Mar 2024 14:11
Last Modified: 09 Mar 2024 14:11
URI: https://pred.uni-regensburg.de/id/eprint/59402

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