Tumor Acidosis

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 6852

Special Issue Editors


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Guest Editor
Department of Radiooncology, Tumor Pathophysiology Group, University Medical Center, Langenbeckstrasse 1, 55131 Mainz, Germany
Interests: tumor blood flow; tumor hypoxia; tumor oxygenation; tumor metabolic microenvironment; tumor acidosis; tumor microcirculation; hypoxia and malignant progression

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Guest Editor
Department of Cancer Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
Interests: define & characterize deregulated pathways with therapeutic relevance in subsets of human cancers

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Institute of Physiology, University of Halle, Magdeburger Strasse 6, 06097 Halle (Saale), Germany

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Central Institute for Translational Cancer Research (TranslaTUM), Klinikum rechts der Isar der Technischen Universität München, 81675 Munich, Germany
Interests: radiation oncology; NK cell based immunotherapies; preclinical models; tumor biomarker; molecular tumor imaging
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Special Issue Information

Dear Colleagues,

Extracellular acidosis (pH < 6.8) is a complex and detrimental trait of most solid malignancies, contributing to distinct alterations in the tumor microenvironment and in the interaction between cancer and stromal cells. Tumor acidosis can lead to malignant progression and negatively influences antitumor therapies, thus leading to poor patient prognosis. Relevant pathomechanisms involved in the acidification process are anaerobic/aerobic glycolysis and enhanced glutaminolysis (through lactate accumulation) combined with poor microcirculatory drainage, enhanced ketogenesis in cancer-associated fibroblasts, ATP hydrolysis, and CO2 production in the Krebs cycle and the pentose phosphate pathway. These pathomechanisms have been repeatedly described in detail during the past two decades, along with their individual and collective operations with hypoxia/HIF-driven traits.

This Special Issue of Cancers will provide a comprehensive overview of the recent investigations and experimental results on the topic “tumor acidosis” including new data on cell signaling, gene expression, stem cell behavior, autophagy, antitumor immune responses, treatment resistance, acidosis-triggered drug release, pH mapping/imaging, and metabolic reprogramming, among others.

The editors hope that these (and possibly other relevant) fields will be we well represented in the contributions to this Special Issue of Cancers.

Prof. Dr. Peter Vaupel
Prof. Dr. Robert J. Gillies
Prof. Dr. Oliver Thews
Prof. Dr. Gabriele Multhoff
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • intratumor pH imaging/mapping, translation into the clinical setting
  • pH and malignant progression
  • pH and treatment resistance
  • pH and immune evasion
  • pH-triggered drug release
  • regulation of transmembrane pH gradients
  • cellular pH sensing
  • tumor acidosis and cell signaling
  • pH and regulation of gene expression
  • acidosis and tumor stem cells

Published Papers (2 papers)

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Research

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24 pages, 6181 KiB  
Article
The Release of Inflammatory Mediators from Acid-Stimulated Mesenchymal Stromal Cells Favours Tumour Invasiveness and Metastasis in Osteosarcoma
by Sofia Avnet, Silvia Lemma, Margherita Cortini, Gemma Di Pompo, Francesca Perut, Maria Veronica Lipreri, Laura Roncuzzi, Marta Columbaro, Costantino Errani, Alessandra Longhi, Nicoletta Zini, Dominique Heymann, Massimo Dominici, Giulia Grisendi, Giulia Golinelli, Lorena Consolino, Dario Livio Longo, Cristina Nanni, Alberto Righi and Nicola Baldini
Cancers 2021, 13(22), 5855; https://doi.org/10.3390/cancers13225855 - 22 Nov 2021
Cited by 14 | Viewed by 3071
Abstract
Osteosarcoma is the most frequent primary malignant bone tumour with an impressive tendency to metastasise. Highly proliferative tumour cells release a remarkable amount of protons into the extracellular space that activates the NF-kB inflammatory pathway in adjacent stromal cells. In this study, we [...] Read more.
Osteosarcoma is the most frequent primary malignant bone tumour with an impressive tendency to metastasise. Highly proliferative tumour cells release a remarkable amount of protons into the extracellular space that activates the NF-kB inflammatory pathway in adjacent stromal cells. In this study, we further validated the correlation between tumour glycolysis/acidosis and its role in metastases. In patients, at diagnosis, we found high circulating levels of inflammatory mediators (IL6, IL8 and miR-136-5p-containing extracellular vesicles). IL6 serum levels significantly correlated with disease-free survival and 18F-FDG PET/CT uptake, an indirect measurement of tumour glycolysis and, hence, of acidosis. In vivo subcutaneous and orthotopic models, co-injected with mesenchymal stromal (MSC) and osteosarcoma cells, formed an acidic tumour microenvironment (mean pH 6.86, as assessed by in vivo MRI-CEST pH imaging). In these xenografts, we enlightened the expression of both IL6 and the NF-kB complex subunit in stromal cells infiltrating the tumour acidic area. The co-injection with MSC also significantly increased lung metastases. Finally, by using 3D microfluidic models, we directly showed the promotion of osteosarcoma invasiveness by acidosis via IL6 and MSC. In conclusion, osteosarcoma-associated MSC react to intratumoural acidosis by triggering an inflammatory response that, in turn, promotes tumour invasiveness at the primary site toward metastasis development. Full article
(This article belongs to the Special Issue Tumor Acidosis)
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Review

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15 pages, 684 KiB  
Review
Chloride Channels and Transporters: Roles beyond Classical Cellular Homeostatic pH or Ion Balance in Cancers
by Hyeong Jae Kim, Peter Chang-Whan Lee and Jeong Hee Hong
Cancers 2022, 14(4), 856; https://doi.org/10.3390/cancers14040856 - 9 Feb 2022
Cited by 11 | Viewed by 2808
Abstract
The canonical roles of chloride channels and chloride-associated transporters have been physiologically determined; these roles include the maintenance of membrane potential, pH balance, and volume regulation and subsequent cellular functions such as autophagy and cellular proliferative processes. However, chloride channels/transporters also play other [...] Read more.
The canonical roles of chloride channels and chloride-associated transporters have been physiologically determined; these roles include the maintenance of membrane potential, pH balance, and volume regulation and subsequent cellular functions such as autophagy and cellular proliferative processes. However, chloride channels/transporters also play other roles, beyond these classical function, in cancerous tissues and under specific conditions. Here, we focused on the chloride channel-associated cancers and present recent advances in understanding the environments of various types of cancer caused by the participation of many chloride channel or transporters families and discuss the challenges and potential targets for cancer treatment. The modulation of chloride channels/transporters might promote new aspect of cancer treatment strategies. Full article
(This article belongs to the Special Issue Tumor Acidosis)
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