Expression of the plasma membrane citrate carrier (pmCiC) in human cancerous tissues-correlation with tumour aggressiveness.

Autor: Schwertner B; Department of Dermatology, University Hospital Regensburg, Regensburg, Germany., Dahdal G; Department of Dermatology, University Hospital Regensburg, Regensburg, Germany., Jagla W; Institute of Pathology Kaufbeuren-Ravensburg, Kaufbeuren, Germany., Grossmann L; Department of Structural Biology, Institute of Biophysics and Physical Biochemistry, University of Regensburg, Regensburg, Germany., Drexler K; Department of Dermatology, University Hospital Regensburg, Regensburg, Germany., Krahn MP; Medical Cell Biology, Internal Medicine D, University Hospital Münster, Münster, Germany., Evert K; Institute of Pathology, University of Regensburg, Regensburg, Germany., Berneburg M; Department of Dermatology, University Hospital Regensburg, Regensburg, Germany., Haferkamp S; Department of Dermatology, University Hospital Regensburg, Regensburg, Germany., Ziegler C; Department of Structural Biology, Institute of Biophysics and Physical Biochemistry, University of Regensburg, Regensburg, Germany., Parkinson EK; Centre for Oral Immunobiology and Regenerative Medicine, Institute of Dentistry, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom., Zahn G; Eternygen GmbH, Berlin, Germany., Mycielska ME; Department of Structural Biology, Institute of Biophysics and Physical Biochemistry, University of Regensburg, Regensburg, Germany., Gaumann A; Institute of Pathology Kaufbeuren-Ravensburg, Kaufbeuren, Germany.
Jazyk: angličtina
Zdroj: Frontiers in cell and developmental biology [Front Cell Dev Biol] 2024 Jul 03; Vol. 12, pp. 1308135. Date of Electronic Publication: 2024 Jul 03 (Print Publication: 2024).
DOI: 10.3389/fcell.2024.1308135
Abstrakt: We have recently shown that cancer cells of various origins take up extracellular citrate through the plasma membrane citrate carrier (pmCiC), a specific plasma membrane citrate transporter. Extracellular citrate is required to support cancer cell metabolism, in particular fatty acid synthesis, mitochondrial activity, protein synthesis and histone acetylation. In addition, cancer cells tend to acquire a metastatic phenotype in the presence of extracellular citrate. Our recent study also showed that cancer-associated stromal cells synthesise and release citrate and that this process is controlled by cancer cells. In the present study, we evaluated the expression of pmCiC, fibroblast activation protein-α (FAP) and the angiogenesis marker cluster of differentiation 31 (CD31) in human cancer tissues of different origins. In the cohort studied, we found no correlation between disease stage and the expression of FAP or CD31. However, we have identified a clear correlation between pmCiC expression in cancer cells and cancer-associated stroma with tumour stage. It can be concluded that pmCiC is increased in cancer cells and in cancer-supporting cells in the tumour microenvironment at the later stages of cancer development, particularly at the metastatic sites. Therefore, pmCiC expression has the potential to serve as a prognostic marker, although further studies are needed.
Competing Interests: MM is an inventor on the Patent Application no. EP15767532.3 and US15/514,255 (status patent pending) “The plasma membrane citrate transporter for use in the diagnosis and treatment of cancer” owned by the University Hospital Regensburg. GZ is an employee and shareholder of Eternygen GmbH. MM is a shareholder of MetaSMIte, Sp. z o.o., Krakow, Poland. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
(Copyright © 2024 Schwertner, Dahdal, Jagla, Grossmann, Drexler, Krahn, Evert, Berneburg, Haferkamp, Ziegler, Parkinson, Zahn, Mycielska and Gaumann.)
Databáze: MEDLINE