Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Advances in Cancer Metabolism and Tumour Microenvironment 2.0

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 32316

Share This Special Issue

Special Issue Editors

Prof. Dr. Karel Smetana, Jr.

E-Mail Website1 Website2 Website3
Guest Editor

1st Faculty Medicine, Institute of Anatomy and BIOCEV, Charles University, Prague 2 and Vestec, Prague, Czech Republic
Interests: tumor microenvironment; cutaneous malignant melanoma; cancer-associated fibroblasts; squamous epithelium; stem cells
Special Issues, Collections and Topics in MDPI journals

Dr. Michal Masarik

E-Mail Website1 Website2
Guest Editor

Department of Pathological Physiology, Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice, 562500 Brno, Czech Republic
Interests: tumor biology; biochemistry and genetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

At the beginning of cancer research, attention was paid primarily to the characteristics of tumour cells themselves; however, the importance of the tumour microenvironment has been revealed gradually. The simple accumulation of mutations in cancer cells was shown to be insufficient for cancer progression and for the formation of metastases. On the other hand, the key mechanisms of carcinogenesis were revealed in cell communication and metabolic interactions in the tumour microenvironment. These interactions are necessary for maintaining the energy and redox balance in cancer cells and encompass literally all stages of tumour development. How cancer cells acquire and use different metabolites and reprogram their microenvironment to support tumour growth is an area of research that can have interesting therapeutic implications and a large impact on public health. Detecting metabolite level alterations in cancers may reveal an Achilles heel of cancer cells in the form of therapeutically targetable metabolic dependencies. Furthermore, because of metabolite alterations, epigenetic and gene expression changes can occur through altered DNA methylation or posttranslational protein modifications. These can lead to finding new applicable cancer biomarkers. Taken together, an altered cellular metabolism is undoubtedly a key hallmark of cancer, and an understanding of cancer metabolism will probably bring novel therapeutic approaches and new hope into cancer treatment.

Prof. Dr. Karel Smetana, Jr.
Dr. Michal Masarik
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

Cancer metabolism
Metabolites
Tumour microenvironment
Cancer treatment
Tumour growth
DNA methylation
Epigenetic plasticity
Hallmarks of cancer

Published Papers (7 papers)

Download All Papers

Research

Jump to: Review

15 pages, 3671 KiB

Open AccessArticle

Thymoquinone Suppresses Angiogenesis in DEN-Induced Hepatocellular Carcinoma by Targeting miR-1-3p

by Samer A. Tadros, Yasmin M. Attia, Nadine W. Maurice, Sally A. Fahim, Fatma M. Abdelwahed, Samar Ibrahim and Osama A. Badary

Int. J. Mol. Sci. 2022, 23(24), 15904; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232415904 - 14 Dec 2022

Cited by 5 | Viewed by 1393

Abstract

Hepatocellular carcinoma (HCC) is characterized by its high vascularity and metastasis. Thymoquinone (TQ), the main bio-active constituent of Nigella sativa, has shown anticancer and hepatoprotective effects. TQ’s anticancer effect is mediated through miRNA regulation. miR-1-3p plays a significant role in various cancers but its role in HCC invasiveness remains poorly understood. Bio-informatics analysis predicted that the 3′-UTR of TIMP3 is a target for miR-1-3p; Rats were equally divided into four groups: Group 1, the negative control; Group 2 received TQ; Group 3 received DEN; and Group 4 received DEN after pretreatment with TQ. The expression of TIMP3, MMP2, MMP9, and VEGF in rats’ liver was determined immunohistochemically. RT-qPCR was used to measure the miR-1-3p level in rats’ liver, and TIMP3, MMP2, MMP9, and VEGF in the HepG2 cells after being transfected with miR-1-3p mimic or inhibitor; In rats pretreated with TQ, a decreased expression of MMP2, MMP9 and VEGF, and increased expression levels of TIMP3 and miR-1-3p were detected. Treating the HepG2 cells with miR-1-3p mimic led to the upregulation of TIMP3 and downregulation of MMP2, MMP9, and VEGF, and showed a significant delay in wound healing; These results suggested that the anti-angiogenic effect of TQ in HCC may be mediated through the regulation of miR-1-3p. Full article

(This article belongs to the Special Issue Advances in Cancer Metabolism and Tumour Microenvironment 2.0)

► Show Figures

Figure 1

15 pages, 2275 KiB

Open AccessArticle

Molecular Characterization of the Dual Effect of the GPER Agonist G-1 in Glioblastoma

by Alex Hirtz, Yann Bailly, Fabien Rech, Julien Pierson, Hélène Dumond and Hélène Dubois-Pot-Schneider

Int. J. Mol. Sci. 2022, 23(22), 14309; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232214309 - 18 Nov 2022

Cited by 4 | Viewed by 1433

Abstract

Glioblastoma (GBM) is the most common primary brain tumor in adults. Despite conventional treatment, consisting of a chirurgical resection followed by concomitant radio–chemotherapy, the 5-year survival rate is less than 5%. Few risk factors are clearly identified, but women are 1.4-fold less affected than men, suggesting that hormone and particularly estrogen signaling could have protective properties. Indeed, a high GPER1 (G-protein-coupled estrogen receptor) expression is associated with better survival, especially in women who produce a greater amount of estrogen. Therefore, we addressed the anti-tumor effect of the GPER agonist G-1 in vivo and characterized its molecular mechanism of action in vitro. First, the antiproliferative effect of G-1 was confirmed in a model of xenografted nude mice. A transcriptome analysis of GBM cells exposed to G-1 was performed, followed by functional analysis of the differentially expressed genes. Lipid and steroid synthesis pathways as well as cell division processes were both affected by G-1, depending on the dose and duration of the treatment. ANGPTL4, the first marker of G-1 exposure in GBM, was identified and validated in primary GBM cells and patient samples. These data strongly support the potential of G-1 as a promising chemotherapeutic compound for the treatment of GBM. Full article

(This article belongs to the Special Issue Advances in Cancer Metabolism and Tumour Microenvironment 2.0)

► Show Figures

Figure 1

20 pages, 3674 KiB

Open AccessArticle

Tumor-Associated Lymphatics Upregulate MHC-II to Suppress Tumor-Infiltrating Lymphocytes

by Claire Y. Li, Hyeung Ju Park, Jinyeon Shin, Jung Eun Baik, Babak J. Mehrara and Raghu P. Kataru

Int. J. Mol. Sci. 2022, 23(21), 13470; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232113470 - 03 Nov 2022

Cited by 3 | Viewed by 1695

Abstract

Steady-state lymphatic endothelial cells (LECs) can induce peripheral tolerance by presenting endogenous antigens on MHC class I (MHC-I) molecules. Recent evidence suggests that lymph node LECs can cross-present tumor antigens on MHC-I to suppress tumor-specific CD8+ T cells. Whether LECs can act as immunosuppressive cells in an MHC-II dependent manner in the local tumor microenvironment (TME) is not well characterized. Using murine heterotopic and spontaneous tumor models, we show that LECs in the TME increase MHC-II expression in the context of increased co-inhibitory signals. We provide evidence that tumor lymphatics in human melanoma and breast cancer also upregulate MHC-II compared to normal tissue lymphatics. In transgenic mice that lack LEC-specific MHC-II expression, heterotopic tumor growth is attenuated, which is associated with increased numbers of tumor-specific CD8+ and effector CD4+ T cells, as well as decreased numbers of T regulatory CD4+ cells in the TME. Mechanistically, we show that murine and human dermal LECs can take up tumor antigens in vitro. Antigen-loaded LECs in vitro can induce antigen-specific proliferation of CD8+ T cells but not CD4+ T cells; however, these proliferated CD8+ T cells have reduced effector function in the presence of antigen-loaded LECs. Taken together, our study suggests LECs can act as immunosuppressive cells in the TME in an MHC-II dependent manner. Whether this is a result of direct tumor antigen presentation on MHC-II requires additional investigation. Full article

(This article belongs to the Special Issue Advances in Cancer Metabolism and Tumour Microenvironment 2.0)

► Show Figures

Figure 1

19 pages, 3806 KiB

Open AccessArticle

Androgen Receptor Expression in the Various Regions of Resected Glioblastoma Multiforme Tumors and in an In Vitro Model

by Donata Simińska, Jan Korbecki, Klaudyna Kojder, Dariusz Jeżewski, Maciej Tarnowski, Patrycja Tomasiak, Katarzyna Piotrowska, Marta Masztalewicz, Agnieszka Kolasa, Dariusz Chlubek and Irena Baranowska-Bosiacka

Int. J. Mol. Sci. 2022, 23(21), 13004; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232113004 - 27 Oct 2022

Cited by 4 | Viewed by 1610

Abstract

Glioblastoma multiforme (GBM) is a malignant glioma, difficult to detect and with the lowest survival rates among gliomas. Its greater incidence among men and its higher survival rate among premenopausal women suggest that it may be associated with the levels of androgens. As androgens stimulate the androgen receptor (AR), which acts as a transcription factor, the aim of this study was the investigate the role of AR in the progression of GBM. The study was conducted on tissues collected from three regions of GBM tumors (tumor core, enhancing tumor region, and peritumoral area). In addition, an in vitro experiment was conducted on U-87 cells under various culture conditions (necrotic, hypoxic, and nutrient-deficient), mimicking the conditions in a tumor. In both of the models, androgen receptor expression was determined at the gene and protein levels, and the results were confirmed by confocal microscopy and immunohistochemistry. AR mRNA expression was higher under nutrient-deficient conditions and lower under hypoxic conditions in vitro. However, there were no differences in AR protein expression. No differences in AR mRNA expression were observed between the tested tumor structures taken from patients. No differences in AR mRNA expression were observed between the men and women. However, AR protein expression in tumors resected from patients was higher in the enhancing tumor region and in the peritumoral area than in the tumor core. In women, higher AR expression was observed in the peritumoral area than in the tumor core. AR expression in GBM tumors did not differ significantly between men and women, which suggests that the higher incidence of GBM in men is not associated with AR expression. In the group consisting of men and women, AR expression varied between the regions of the tumor: AR expression was higher in the enhancing tumor region and in the peritumoral area than in the tumor core, showing a dependence on tumor conditions (hypoxia and insufficient nutrient supply). Full article

(This article belongs to the Special Issue Advances in Cancer Metabolism and Tumour Microenvironment 2.0)

► Show Figures

Figure 1

Review

Jump to: Research

14 pages, 907 KiB

Open AccessReview

Fatty Acid Metabolism in Ovarian Cancer: Therapeutic Implications

by Hyunho Yoon and Sanghoon Lee

Int. J. Mol. Sci. 2022, 23(4), 2170; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23042170 - 16 Feb 2022

Cited by 31 | Viewed by 9180

Abstract

Ovarian cancer is the most malignant gynecological tumor. Previous studies have reported that metabolic alterations resulting from deregulated lipid metabolism promote ovarian cancer aggressiveness. Lipid metabolism involves the oxidation of fatty acids, which leads to energy generation or new lipid metabolite synthesis. The upregulation of fatty acid synthesis and related signaling promote tumor cell proliferation and migration, and, consequently, lead to poor prognosis. Fatty acid-mediated lipid metabolism in the tumor microenvironment (TME) modulates tumor cell immunity by regulating immune cells, including T cells, B cells, macrophages, and natural killer cells, which play essential roles in ovarian cancer cell survival. Here, the types and sources of fatty acids and their interactions with the TME of ovarian cancer have been reviewed. Additionally, this review focuses on the role of fatty acid metabolism in tumor immunity and suggests that fatty acid and related lipid metabolic pathways are potential therapeutic targets for ovarian cancer. Full article

(This article belongs to the Special Issue Advances in Cancer Metabolism and Tumour Microenvironment 2.0)

► Show Figures

Figure 1

18 pages, 2470 KiB

Open AccessReview

Cancer as a Metabolic Disorder

by Jones Gyamfi, Jinyoung Kim and Junjeong Choi

Int. J. Mol. Sci. 2022, 23(3), 1155; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031155 - 21 Jan 2022

Cited by 56 | Viewed by 13726

Abstract

Cancer has long been considered a genetic disease characterized by a myriad of mutations that drive cancer progression. Recent accumulating evidence indicates that the dysregulated metabolism in cancer cells is more than a hallmark of cancer but may be the underlying cause of the tumor. Most of the well-characterized oncogenes or tumor suppressor genes function to sustain the altered metabolic state in cancer. Here, we review evidence supporting the altered metabolic state in cancer including key alterations in glucose, glutamine, and fatty acid metabolism. Unlike genetic alterations that do not occur in all cancer types, metabolic alterations are more common among cancer subtypes and across cancers. Recognizing cancer as a metabolic disorder could unravel key diagnostic and treatments markers that can impact approaches used in cancer management. Full article

(This article belongs to the Special Issue Advances in Cancer Metabolism and Tumour Microenvironment 2.0)

► Show Figures

Figure 1

22 pages, 1808 KiB

Open AccessReview

Multiple Faces of the Glioblastoma Microenvironment

by Alina Simona Șovrea, Bianca Boșca, Carmen Stanca Melincovici, Anne-Marie Constantin, Andreea Crintea, Mariana Mărginean, Eleonora Dronca, Mihaela Elena Jianu, Rada Suflețel, Diana Gonciar, Maria Bungărdean and Carmen-Bianca Crivii

Int. J. Mol. Sci. 2022, 23(2), 595; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23020595 - 06 Jan 2022

Cited by 6 | Viewed by 2443

Abstract

The tumor microenvironment is a highly dynamic accumulation of resident and infiltrating tumor cells, responsible for growth and invasion. The authors focused on the leading-edge concepts regarding the glioblastoma microenvironment. Due to the fact that the modern trend in the research and treatment of glioblastoma is represented by multiple approaches that target not only the primary tumor but also the neighboring tissue, the study of the microenvironment in the peritumoral tissue is an appealing direction for current and future therapies. Full article

(This article belongs to the Special Issue Advances in Cancer Metabolism and Tumour Microenvironment 2.0)

► Show Figures