Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.4
5.2
Journals
Cancers
Special Issues
At the Crossroads of Tumor Microenvironment and Metabolism
share announcement

At the Crossroads of Tumor Microenvironment and Metabolism

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 16996

Special Issue Editors

Prof. Dr. Olivier Feron

E-Mail Website
Guest Editor
Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, 1200 Brussels, Belgium
Interests: microenvironment; acidosis; hypoxia; lipid metabolism
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Mattias Belting

E-Mail Website
Guest Editor
Department of Clinical Sciences, Oncology and Pathology, Lund University, Lund, Sweden

Special Issue Information

Dear Colleagues,

The tumor microenvironment (TME) consists in the complex mixture of cancer cells, stromal cells and extracellular matrix that all together form a biological milieu characterized by heterogenous pO2 and pH distribution. There is no doubt that the distance from normative values of the two latter physico-chemical characteristics is caused by the uncontrolled growth of cancer cells that benefit from the presence of stromal cells such as fibroblasts or endothelial cells. However it is also well accepted that the occurrence of hypoxia and acidification within tumor areas will in turn promote phenotypical alterations in cancer cells and cancer-associated immune cells. Metabolic rewiring is probably the most well known consequence of the specific environment in which cancer cells and stromal cells have to live together. In the last decade, TME and associated altered metabolism were documented to influence and sometimes to drive cancer cell invasiveness, immunosuppression and drug resistance, often independently of the oncogenic status of cancer cells. This triad accounts for most of fatal outcomes for cancer patients. Thus, further comprehensive research is required to tackle the interplay between metabolism and the cellular and non-cellular components of TME, and how this can lead to the identification of innovative therapeutic targets.

This special issue on “At the Crossroads of Tumor Microenvironment and Metabolism” welcomes both original and review articles.

Prof. Dr. Olivier Feron
Prof. Dr. Mattias Belting
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

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

  • microenvironment
  • hypoxia
  • acidosis
  • stromal cells
  • immune cells
  • metabolism
  • lipids
  • invasiveness
  • Immune escape
  • drug resistance

Published Papers (5 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

18 pages, 5920 KiB  
Article
Serum Levels of the Cytokine TWEAK Are Associated with Metabolic Status in Patients with Prostate Cancer and Modulate Cancer Cell Lipid Metabolism In Vitro
by Antonio Altuna-Coy, Xavier Ruiz-Plazas, Marta Alves-Santiago, José Segarra-Tomás and Matilde R. Chacón
Cancers 2021, 13(18), 4688; https://doi.org/10.3390/cancers13184688 - 18 Sep 2021
Cited by 2 | Viewed by 2390
Abstract
Soluble TWEAK (sTWEAK) has been proposed as a prognostic biomarker of prostate cancer (PCa). We found that reduced serum levels of sTWEAK, together with higher levels of prostate-specific antigen and a higher HOMA-IR index, are independent predictors of PCa. We also showed that [...] Read more.
Soluble TWEAK (sTWEAK) has been proposed as a prognostic biomarker of prostate cancer (PCa). We found that reduced serum levels of sTWEAK, together with higher levels of prostate-specific antigen and a higher HOMA-IR index, are independent predictors of PCa. We also showed that sTWEAK stimulus failed to alter the expression of glucose transporter genes (SLC2A4 and SLC2A1), but significantly reduced the expression of glucose metabolism-related genes (PFK, HK1 and PDK4) in PCa cells. The sTWEAK stimulation of PC-3 cells significantly increased the expression of the genes related to lipogenesis (ACACA and FASN), lipolysis (CPT1A and PNPLA2), lipid transport (FABP4 and CD36) and lipid regulation (SREBP-1 and PPARG) and increased the lipid uptake. Silencing the TWEAK receptor (Fn14) in PC-3 cells confirmed the observed lipid metabolic effects, as shown by the downregulation of ACACA, FASN, CPT1A, PNPLA2, FABP4, CD36, SREBP-1 and PPARG expression, which was paralleled by a reduction of FASN, CPT1A and FABP4 protein expression. Specific-signaling inhibitor assays show that ERK1/2 and AKT (ser473) phosphorylation can regulate lipid metabolism-related genes in PCa cells, pointing to the AKT locus as a possible target for PCa. Overall, our data support sTWEAK/Fn14 axis as a potential therapeutic target for PCa. Full article
(This article belongs to the Special Issue At the Crossroads of Tumor Microenvironment and Metabolism)
►▼ Show Figures

Figure 1

28 pages, 5717 KiB  
Article
VDAC1 Silencing in Cancer Cells Leads to Metabolic Reprogramming That Modulates Tumor Microenvironment
by Erez Zerbib, Tasleem Arif, Anna Shteinfer-Kuzmine, Vered Chalifa-Caspi and Varda Shoshan-Barmatz
Cancers 2021, 13(11), 2850; https://doi.org/10.3390/cancers13112850 - 07 Jun 2021
Cited by 10 | Viewed by 4061
Abstract
The tumor microenvironment (TME) plays an important role in cell growth, proliferation, migration, immunity, malignant transformation, and apoptosis. Thus, better insight into tumor–host interactions is required. Most of these processes involve the metabolic reprogramming of cells. Here, we focused on this reprogramming in [...] Read more.
The tumor microenvironment (TME) plays an important role in cell growth, proliferation, migration, immunity, malignant transformation, and apoptosis. Thus, better insight into tumor–host interactions is required. Most of these processes involve the metabolic reprogramming of cells. Here, we focused on this reprogramming in cancerous cells and its effect on the TME. A major limitation in the study of tumor–host interactions is the difficulty in separating cancerous from non-cancerous signaling pathways within a tumor. Our strategy involved specifically silencing the expression of VDAC1 in the mitochondria of human-derived A549 lung cancer xenografts in mice, but not in the mouse-derived cells of the TME. Next-generation sequencing (NGS) analysis allows distinguishing the human or mouse origin of genes, thus enabling the separation of the bidirectional cross-talk between the TME and malignant cells. We demonstrate that depleting VDAC1 in cancer cells led to metabolic reprogramming, tumor regression, and the disruption of tumor–host interactions. This was reflected in the altered expression of a battery of genes associated with TME, including those involved in extracellular matrix organization and structure, matrix-related peptidases, angiogenesis, intercellular interacting proteins, integrins, and growth factors associated with stromal activities. We show that metabolic rewiring upon mitochondrial VDAC1 silencing in cancer cells affected several components of the TME, such as structural protein matrix metalloproteinases and Lox, and elicited a stromal response resembling the reaction to a foreign body in wound healing. As tumor progression requires a cooperative interplay between the host and cancer cells, and the ECM is intensively remodeled during cancer progression, VDAC1 depletion induced metabolic reprogramming that targeted both tumor cells and resulted in the alteration of the whole spectrum of TME-related genes, affecting the reciprocal feedback between ECM molecules, host cells, and cancer cells. Thus, VDAC1 depletion using si-VDAC1 represents therapeutic potential, inhibiting cancer cell proliferation and also inducing the modulation of TME components, which influences cancer progression, migration, and invasion. Full article
(This article belongs to the Special Issue At the Crossroads of Tumor Microenvironment and Metabolism)
►▼ Show Figures

Figure 1

24 pages, 5456 KiB  
Article
Exploring Metabolic Adaptations to the Acidic Microenvironment of Osteosarcoma Cells Unveils Sphingosine 1-Phosphate as a Valuable Therapeutic Target
by Margherita Cortini, Andrea Armirotti, Marta Columbaro, Dario Livio Longo, Gemma Di Pompo, Elena Cannas, Alessandra Maresca, Costantino Errani, Alessandra Longhi, Alberto Righi, Valerio Carelli, Nicola Baldini and Sofia Avnet
Cancers 2021, 13(2), 311; https://doi.org/10.3390/cancers13020311 - 15 Jan 2021
Cited by 15 | Viewed by 2908
Abstract
Acidity is a key player in cancer progression, modelling a microenvironment that prevents immune surveillance and enhances invasiveness, survival, and drug resistance. Here, we demonstrated in spheroids from osteosarcoma cell lines that the exposure to acidosis remarkably caused intracellular lipid droplets accumulation. Lipid [...] Read more.
Acidity is a key player in cancer progression, modelling a microenvironment that prevents immune surveillance and enhances invasiveness, survival, and drug resistance. Here, we demonstrated in spheroids from osteosarcoma cell lines that the exposure to acidosis remarkably caused intracellular lipid droplets accumulation. Lipid accumulation was also detected in sarcoma tissues in close proximity to tumor area that express the acid-related biomarker LAMP2. Acid-induced lipid droplets-accumulation was not functional to a higher energetic request, but rather to cell survival. As a mechanism, we found increased levels of sphingomyelin and secretion of the sphingosine 1-phosphate, and the activation of the associated sphingolipid pathway and the non-canonical NF-ĸB pathway, respectively. Moreover, decreasing sphingosine 1-phosphate levels (S1P) by FTY720 (Fingolimod) impaired acid-induced tumor survival and migration. As a confirmation of the role of S1P in osteosarcoma, we found S1P high circulating levels (30.8 ± 2.5 nmol/mL, n = 17) in the serum of patients. Finally, when we treated osteosarcoma xenografts with FTY720 combined with low-serine/glycine diet, both lipid accumulation (as measured by magnetic resonance imaging) and tumor growth were greatly inhibited. For the first time, this study profiles the lipidomic rearrangement of sarcomas under acidic conditions, suggesting the use of anti-S1P strategies in combination with standard chemotherapy. Full article
(This article belongs to the Special Issue At the Crossroads of Tumor Microenvironment and Metabolism)
►▼ Show Figures

Figure 1

17 pages, 2287 KiB  
Article
Acidosis-Induced TGF-β2 Production Promotes Lipid Droplet Formation in Dendritic Cells and Alters Their Potential to Support Anti-Mesothelioma T Cell Response
by Natalia Trempolec, Charline Degavre, Bastien Doix, Davide Brusa, Cyril Corbet and Olivier Feron
Cancers 2020, 12(5), 1284; https://doi.org/10.3390/cancers12051284 - 19 May 2020
Cited by 26 | Viewed by 3325
Abstract
For poorly immunogenic tumors such as mesothelioma there is an imperious need to understand why antigen-presenting cells such as dendritic cells (DCs) are not prone to supporting the anticancer T cell response. The tumor microenvironment (TME) is thought to be a major contributor [...] Read more.
For poorly immunogenic tumors such as mesothelioma there is an imperious need to understand why antigen-presenting cells such as dendritic cells (DCs) are not prone to supporting the anticancer T cell response. The tumor microenvironment (TME) is thought to be a major contributor to this DC dysfunction. We have reported that the acidic TME component promotes lipid droplet (LD) formation together with epithelial-to-mesenchymal transition in cancer cells through autocrine transforming growth factor-β2 (TGF-β2) signaling. Since TGF-β is also a master regulator of immune tolerance, we have here examined whether acidosis can impede immunostimulatory DC activity. We have found that exposure of mesothelioma cells to acidosis promotes TGF-β2 secretion, which in turn leads to LD accumulation and profound metabolic rewiring in DCs. We have further documented how DCs exposed to the mesothelioma acidic milieu make the anticancer vaccine less efficient in vivo, with a reduced extent of both DC migratory potential and T cell activation. Interestingly, inhibition of TGF-β2 signaling and diacylglycerol O-acyltransferase (DGAT), the last enzyme involved in triglyceride synthesis, led to a significant restoration of DC activity and anticancer immune response. In conclusion, our study has identified that acidic mesothelioma milieu drives DC dysfunction and altered T cell response through pharmacologically reversible TGF-β2-dependent mechanisms. Full article
(This article belongs to the Special Issue At the Crossroads of Tumor Microenvironment and Metabolism)
►▼ Show Figures

Figure 1

Review

Jump to: Research

31 pages, 1540 KiB  
Review
Melanoma Progression under Obesity: Focus on Adipokines
by Joanna Olszańska, Katarzyna Pietraszek-Gremplewicz and Dorota Nowak
Cancers 2021, 13(9), 2281; https://doi.org/10.3390/cancers13092281 - 10 May 2021
Cited by 12 | Viewed by 3340
Abstract
Obesity is a growing problem in the world and is one of the risk factors of various cancers. Among these cancers is melanoma, which accounts for the majority of skin tumor deaths. Current studies are looking for a correlation between obesity and melanoma. [...] Read more.
Obesity is a growing problem in the world and is one of the risk factors of various cancers. Among these cancers is melanoma, which accounts for the majority of skin tumor deaths. Current studies are looking for a correlation between obesity and melanoma. They suspect that a potential cause of its development is connected to the biology of adipokines, active molecules secreted by adipose tissue. Under physiological conditions, adipokines control many processes, including lipid and glucose homeostasis, insulin sensitivity, angiogenesis, and inflammations. However, when there is an increased amount of fat in the body, their secretion is dysregulated. This article reviews the current knowledge of the effect of adipokines on melanoma growth. This work focuses on the molecular pathways by which adipose tissue secreted molecules modify the angiogenesis, migration, invasion, proliferation, and death of melanoma cells. We also discuss the role of these factors as markers of incidence, metastasis, and melanoma patient survival. Understanding the functions of adipokines will lead to knowledge of whether and how obesity promotes melanoma growth. Further studies may contribute to the innovations of therapies and the use of adipokines as predictive and/or prognostic biomarkers. Full article
(This article belongs to the Special Issue At the Crossroads of Tumor Microenvironment and Metabolism)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-5
Back to TopTop