Stress Responses in Tumors and The Tumor Microenvironment

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 July 2015) | Viewed by 23951

Special Issue Editor


E-Mail Website
Guest Editor
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
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite progress in high precision image-guided radiation technology and innovative hypo-fractionated radiotherapeutic concepts the clinical outcome of radiotherapy in locally advanced and metastasized tumors is still not satisfying. Due to a chaotic tumor vasculature a hostile tumor microenvironment develops which may be involved in the hypoxia-mediated radioresistance of tumor cells. This special issue of Cancers seeks for articles that are addressing mechanisms which are improving the understanding of stress responses in tumors and the tumor microenvironment and signalling pathways that are related to radioresistance.

Prof. Dr. Gabriele Multhoff
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. 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

  • radiation oncology
  • metastases
  • radioresistance
  • tumor stress responses
  • tumor microenvironment
  • hypoxia

Published Papers (4 papers)

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

Research

Jump to: Review

2106 KiB  
Article
Deficiency of iPLA2β Primes Immune Cells for Proinflammation: Potential Involvement in Age-Related Mesenteric Lymph Node Lymphoma
by Johannes Inhoffen, Sabine Tuma-Kellner, Beate Straub, Wolfgang Stremmel and Walee Chamulitrat
Cancers 2015, 7(4), 2427-2442; https://doi.org/10.3390/cancers7040901 - 9 Dec 2015
Cited by 14 | Viewed by 4305
Abstract
Proinflammation can predispose the body to autoimmunity and cancer. We have reported that iPLA2β−/− mice are susceptible to autoimmune hepatitis and colitis. Here we determined whether cytokine release by immune cells could be affected by iPLA2β deficiency alone [...] Read more.
Proinflammation can predispose the body to autoimmunity and cancer. We have reported that iPLA2β−/− mice are susceptible to autoimmune hepatitis and colitis. Here we determined whether cytokine release by immune cells could be affected by iPLA2β deficiency alone or combined with CD95/FasL-antibody treatment in vivo. We also determined whether cancer risk could be increased in aged mutant mice. Immune cells were isolated from 3-month old male WT and iPLA2β−/− mice, and some were injected with anti-CD95/FasL antibody for 6 h. Kupffer cells (KC) or splenocytes and liver lymphocytes were stimulated in vitro by lipopolysaccharide or concanavalinA, respectively. Whole-body iPLA2β deficiency caused increased apoptosis in liver, spleen, and mesenteric lymph node (MLN). KC from mutant mice showed suppressed release of TNFα and IL-6, while their splenocytes secreted increased levels of IFNγ and IL-17a. Upon CD95/FasL activation, the mutant KC in turn showed exaggerated cytokine release, this was accompanied by an increased release of IFNγ and IL-17a by liver lymphocytes. Aged iPLA2β−/− mice did not show follicular MLN lymphoma commonly seen in aged C57/BL6 mice. Thus, iPLA2β deficiency renders M1- and Th1/Th17-proinflammation potentially leading to a reduction in age-related MLN lymphoma during aging. Full article
(This article belongs to the Special Issue Stress Responses in Tumors and The Tumor Microenvironment)
Show Figures

Figure 1

Review

Jump to: Research

646 KiB  
Review
Stress Response Leading to Resistance in Glioblastoma—The Need for Innovative Radiotherapy (iRT) Concepts
by Stephanie E. Combs, Thomas E. Schmid, Peter Vaupel and Gabriele Multhoff
Cancers 2016, 8(1), 15; https://doi.org/10.3390/cancers8010015 - 13 Jan 2016
Cited by 23 | Viewed by 6127
Abstract
Glioblastoma (GBM) is the most common and most aggressive malignant primary brain tumor in adults. In spite of multimodal therapy concepts, consisting of surgery, radiotherapy and chemotherapy, the median survival, merely 15–18 months, is still poor. Mechanisms for resistance of GBM to radio(chemo)therapy [...] Read more.
Glioblastoma (GBM) is the most common and most aggressive malignant primary brain tumor in adults. In spite of multimodal therapy concepts, consisting of surgery, radiotherapy and chemotherapy, the median survival, merely 15–18 months, is still poor. Mechanisms for resistance of GBM to radio(chemo)therapy are not fully understood yet and due to the genetic heterogeneity within the tumor including radiation-resistant tumor stem cells, there are several factors leading to therapy failure. Recent research revealed that, hypoxia during radiation and miRNAs may adversely affect the therapeutic response to radiotherapy. Further molecular alterations and prognostic markers like the DNA-repair protein O6-methylguanine-DNA methyltransferase (MGMT), anti-apoptotic molecular chaperones, and/or the activity of aldehyde dehydrogenase 1 (ALDH1) have also been identified to play a role in the sensitivity to cytostatic agents. Latest approaches in the field of radiotherapy to use particle irradiation or dose escalation strategies including modern molecular imaging, however, need further evaluation with regard to long-term outcome. In this review we focus on current information about the mechanisms and markers that mediate resistance to radio(chemo)therapy, and discuss the opportunities of Innovative Radiotherapy (iRT) concepts to improve treatment options for GBM patients. Full article
(This article belongs to the Special Issue Stress Responses in Tumors and The Tumor Microenvironment)
Show Figures

Figure 1

585 KiB  
Review
Diverse Mechanisms of Sp1-Dependent Transcriptional Regulation Potentially Involved in the Adaptive Response of Cancer Cells to Oxygen-Deficient Conditions
by Shiro Koizume and Yohei Miyagi
Cancers 2016, 8(1), 2; https://doi.org/10.3390/cancers8010002 - 23 Dec 2015
Cited by 26 | Viewed by 7410
Abstract
The inside of a tumor often contains a hypoxic area caused by a limited supply of molecular oxygen due to aberrant vasculature. Hypoxia-inducible factors (HIFs) are major transcription factors that are required for cancer cells to adapt to such stress conditions. HIFs, complexed [...] Read more.
The inside of a tumor often contains a hypoxic area caused by a limited supply of molecular oxygen due to aberrant vasculature. Hypoxia-inducible factors (HIFs) are major transcription factors that are required for cancer cells to adapt to such stress conditions. HIFs, complexed with the aryl hydrocarbon receptor nuclear translocator, bind to and activate target genes as enhancers of transcription. In addition to this common mechanism, the induction of the unfolded protein response and mTOR signaling in response to endoplasmic reticulum stress is also known to be involved in the adaptation to hypoxia conditions. Sp1 is a ubiquitously-expressed transcription factor that plays a vital role in the regulation of numerous genes required for normal cell function. In addition to the well-characterized stress response mechanisms described above, increasing experimental evidence suggests that Sp1 and HIFs collaborate to drive gene expression in cancer cells in response to hypoxia, thereby regulating additional adaptive responses to cellular oxygen deficiency. However, these characteristics of Sp1 and their biological merits have not been summarized. In this review, we will discuss the diverse mechanisms of transcriptional regulation by Sp1 and their potential involvement in the adaptive response of cancer cells to hypoxic tumor microenvironments. Full article
(This article belongs to the Special Issue Stress Responses in Tumors and The Tumor Microenvironment)
Show Figures

Figure 1

612 KiB  
Review
Hepatocyte Growth Factor from a Clinical Perspective: A Pancreatic Cancer Challenge
by Wasia Rizwani, Amanda E. Allen and Jose G. Trevino
Cancers 2015, 7(3), 1785-1805; https://doi.org/10.3390/cancers7030861 - 3 Sep 2015
Cited by 21 | Viewed by 5493
Abstract
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and incidence rates are rising. Both detection and treatment options for pancreatic cancer are limited, providing a less than 5% five-year survival advantage. The need for new biomarkers for [...] Read more.
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and incidence rates are rising. Both detection and treatment options for pancreatic cancer are limited, providing a less than 5% five-year survival advantage. The need for new biomarkers for early detection and treatment of pancreatic cancer demands the efficient translation of bench knowledge to provide clinical benefit. One source of therapeutic resistance is the pancreatic tumor microenvironment, which is characterized by desmoplasia and hypoxia making it less conducive to current therapies. A major factor regulating desmoplasia and subsequently promoting chemoresistance in pancreatic cancer is hepatocyte growth factor (HGF), the sole ligand for c-MET (mesenchymal-epithelial transition), an epithelial tyrosine kinase receptor. Binding of HGF to c-MET leads to receptor dimerization and autophosphorylation resulting in the activation of multiple cellular processes that support cancer progression. Inhibiting activation of c-MET in cancer cells, in combination with other approaches for reducing desmoplasia in the tumor microenvironment, might significantly improve the success of chemotherapy. Therefore, HGF makes a potent novel target for developing therapeutic strategies in combination with existing drugs for treating pancreatic adenocarcinoma. This review provides a comprehensive analysis of HGF and its promising potential as a chemotherapeutic target for pancreatic cancer. Full article
(This article belongs to the Special Issue Stress Responses in Tumors and The Tumor Microenvironment)
Show Figures

Figure 1

Back to TopTop