ijms-logo

Journal Browser

Journal Browser

Oxygen Regulation in Cancer

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

Deadline for manuscript submissions: closed (28 February 2019) | Viewed by 25142

Special Issue Editors

Department of Radiotherapy (MAASTRO)/GROW, School for Developmental Biology and Oncology, Maastricht University, The Netherlands
Interests: tumor microenvironment and treatment resistance; hypoxia; HIF; Notch signaling; cancer stem cells
Special Issues, Collections and Topics in MDPI journals
Department of Radiotherapy, GROW—School for Oncology and Developmental Biology, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands
Interests: hypoxia; autophagy; extracellular vesicles; unfolded protein response
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Oxygen has been fundamental to most life on our planet for the past 2.5 billion years, and almost all species have evolved highly-conserved oxygen sensing pathways to utilize oxygen as their most important source for energy. Cells respond to physiological changes in oxygen levels by adapting their cellular metabolism, inducing different cell fates, activating proliferation or activating cell survival and cell death mechanisms. Pathological changes in oxygen demand, supply or sensing are a hallmark of locally advanced solid tumors. Intratumoral hypoxia arises during rapid tumor growth when the diffusion distance between normal blood vasculature and core of the tumor becomes limiting and because tumors have irregular defective vascularization. Intratumoral hypoxia is a dynamic feature that strongly contributes to inter and intra tumor heterogeneity, and is associated with reduced treatment response and poor outcome. Hence, tumor hypoxia is a tumor microenvironment selective therapeutic target. Despite the overwhelming evidence for a role of hypoxia in poor patient outcome the results of clinical trials with hypoxia modifying agents—with the exception of Nimorazole—have been largely negative. Thus, there is important need to summarize the latest on oxygen regulation in cancer cells to develop new strategies to better harness tumor hypoxia in cancer to improve outcome.

This Special Issue brings together specialists discussing the basic mechanisms on oxygen sensing and signaling in mammalian cells, the metabolism and transcriptional programs regulated by hypoxia, the clinical consequences of intratumoral hypoxia and current approaches to detect and target hypoxia in tumors.

Prof. Dr. Marc A.G.G. Vooijs
Asscoc. Prof. Kasper M. Rouschop
Guest Editor

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

  • Tumor hypoxia
  • Hypoxia inducible Factor
  • Tumor cell metabolism
  • Hypoxic modification
  • Hypoxia activated prodrugs
  • Therapy resistance
  • Cancer hallmark
  • Cellular adaptation

Published Papers (3 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

15 pages, 7908 KiB  
Article
MDA-MB-231 Breast Cancer Cells and Their CSC Population Migrate Towards Low Oxygen in a Microfluidic Gradient Device
by Jelle J. F. Sleeboom, Jaap M. J. Den Toonder and Cecilia M. Sahlgren
Int. J. Mol. Sci. 2018, 19(10), 3047; https://doi.org/10.3390/ijms19103047 - 06 Oct 2018
Cited by 24 | Viewed by 4601
Abstract
Most cancer deaths are caused by secondary tumors formed through metastasis, yet due to our limited understanding of this process, prevention remains a major challenge. Recently, cancer stem cells (CSCs) have been proposed as the source of metastases, but only little is known [...] Read more.
Most cancer deaths are caused by secondary tumors formed through metastasis, yet due to our limited understanding of this process, prevention remains a major challenge. Recently, cancer stem cells (CSCs) have been proposed as the source of metastases, but only little is known about their migratory behavior. Oxygen gradients in the tumor have been linked to directional migration of breast cancer cells. Here, we present a method to study the effect of oxygen gradients on the migratory behavior of breast CSCs using a microfluidic device. Our chip contains a chamber in which an oxygen gradient can be generated between hypoxic (<1%) and ambient (21%) conditions. We tracked the migration of CSCs obtained from MDA-MB-231 breast cancer cells, and found that their migration patterns do not differ from the average MDA-MB-231 population. Surprisingly, we found that the cells migrate towards low oxygen levels, in contrast with an earlier study. We hypothesize that in our device, migration is exclusively due to the pure oxygen gradient, whereas the effects of oxygen in earlier work were obscured by additional cues from the tumor microenvironment (e.g., nutrients and metabolites). These results open new research directions into the role of oxygen in directing cancer and CSC migration. Full article
(This article belongs to the Special Issue Oxygen Regulation in Cancer)
Show Figures

Graphical abstract

Review

Jump to: Research

27 pages, 4844 KiB  
Review
Primary Cilium in Cancer Hallmarks
by Lucilla Fabbri, Frédéric Bost and Nathalie M. Mazure
Int. J. Mol. Sci. 2019, 20(6), 1336; https://doi.org/10.3390/ijms20061336 - 16 Mar 2019
Cited by 57 | Viewed by 8579
Abstract
The primary cilium is a solitary, nonmotile and transitory appendage that is present in virtually all mammalian cells. Our knowledge of its ultrastructure and function is the result of more than fifty years of research that has dramatically changed our perspectives on the [...] Read more.
The primary cilium is a solitary, nonmotile and transitory appendage that is present in virtually all mammalian cells. Our knowledge of its ultrastructure and function is the result of more than fifty years of research that has dramatically changed our perspectives on the primary cilium. The mutual regulation between ciliogenesis and the cell cycle is now well-recognized, as well as the function of the primary cilium as a cellular “antenna” for perceiving external stimuli, such as light, odorants, and fluids. By displaying receptors and signaling molecules, the primary cilium is also a key coordinator of signaling pathways that converts extracellular cues into cellular responses. Given its critical tasks, any defects in primary cilium formation or function lead to a wide spectrum of diseases collectively called “ciliopathies”. An emerging role of primary cilium is in the regulation of cancer development. In this review, we seek to describe the current knowledge about the influence of the primary cilium in cancer progression, with a focus on some of the events that cancers need to face to sustain survival and growth in hypoxic microenvironment: the cancer hallmarks. Full article
(This article belongs to the Special Issue Oxygen Regulation in Cancer)
Show Figures

Graphical abstract

13 pages, 1151 KiB  
Review
HIF-1-Dependent Reprogramming of Glucose Metabolic Pathway of Cancer Cells and Its Therapeutic Significance
by Ayako Nagao, Minoru Kobayashi, Sho Koyasu, Christalle C. T. Chow and Hiroshi Harada
Int. J. Mol. Sci. 2019, 20(2), 238; https://doi.org/10.3390/ijms20020238 - 09 Jan 2019
Cited by 275 | Viewed by 11565
Abstract
Normal cells produce adenosine 5′-triphosphate (ATP) mainly through mitochondrial oxidative phosphorylation (OXPHOS) when oxygen is available. Most cancer cells, on the other hand, are known to produce energy predominantly through accelerated glycolysis, followed by lactic acid fermentation even under normoxic conditions. This metabolic [...] Read more.
Normal cells produce adenosine 5′-triphosphate (ATP) mainly through mitochondrial oxidative phosphorylation (OXPHOS) when oxygen is available. Most cancer cells, on the other hand, are known to produce energy predominantly through accelerated glycolysis, followed by lactic acid fermentation even under normoxic conditions. This metabolic phenomenon, known as aerobic glycolysis or the Warburg effect, is less efficient compared with OXPHOS, from the viewpoint of the amount of ATP produced from one molecule of glucose. However, it and its accompanying pathway, the pentose phosphate pathway (PPP), have been reported to provide advantages for cancer cells by producing various metabolites essential for proliferation, malignant progression, and chemo/radioresistance. Here, focusing on a master transcriptional regulator of adaptive responses to hypoxia, the hypoxia-inducible factor 1 (HIF-1), we review the accumulated knowledge on the molecular basis and functions of the Warburg effect and its accompanying pathways. In addition, we summarize our own findings revealing that a novel HIF-1-activating factor enhances the antioxidant capacity and resultant radioresistance of cancer cells though reprogramming of the glucose metabolic pathway. Full article
(This article belongs to the Special Issue Oxygen Regulation in Cancer)
Show Figures

Figure 1

Back to TopTop