The Cross Talk between Cancer Stem Cells/Cancer Initiating Cells and Tumor Microenvironment: The Missing Piece of the Puzzle for the Efficient Targeting of these Cells with Immunotherapy
AbstractCancer Stem Cells/Cancer Initiating Cells (CSCs/CICs) is a rare sub-population within a tumor that is responsible for tumor formation, progression and resistance to therapies. The interaction between CSCs/CICs and tumor microenvironment (TME) can sustain “stemness” properties and promote their survival and plasticity. This cross-talk is also pivotal in regulating and modulating CSC/CIC properties. This review will provide an overview of the mechanisms underlying the mutual interaction between CSCs/CICs and TME. Particular focus will be dedicated to the immunological profile of CSCs/CICs and its role in orchestr...
Source: Cancer Microenvironment - November 21, 2019 Category: Cancer & Oncology Source Type: research

Cross-Talk Between circRNAs and mRNAs Modulates MiRNA-mediated Circuits and Affects Melanoma Plasticity
AbstractCircularRNAs (circRNAs) are non-coding RNAs which compete for microRNA (miRNA) binding, influencing the abundance and stability of other RNA species. Herein we have investigated the effect of circRNAs on the mir200-ZEB1 feedback loop in relationship with the aggressiveness of human melanoma cells. We first compared the level of expression of key factors in the mir200-ZEB1 feedback loop in primary human melanoma cells compared with their matching metastatic one and found a correlation between the aggressiveness of the cells and the level of expression of ZEB1 and SNAI1. We also analyzed factors in the mir200-ZEB1 fe...
Source: Cancer Microenvironment - November 15, 2019 Category: Cancer & Oncology Source Type: research

The Concomitant Expression of Human Endogenous Retroviruses and Embryonic Genes in Cancer Cells under Microenvironmental Changes is a Potential Target for Antiretroviral Drugs
AbstractIn our genomes there are thousands of copies of human endogenous retroviruses (HERVs) originated from the integration of exogenous retroviruses that infected germ line cells millions of years ago, and currently an altered expression of this elements has been associated to the onset, progression and acquisition of aggressiveness features of many cancers. The transcriptional reactivation of HERVs is mainly an effect of their responsiveness to some factors in cell microenvironment, such as nutrients, hormones and cytokines. We have already demonstrated that, under pressure of microenvironmental changes, HERV-K (HML-2)...
Source: Cancer Microenvironment - November 4, 2019 Category: Cancer & Oncology Source Type: research

Tumor-Infiltrating Immunosuppressive Cells in Cancer-Cell Plasticity, Tumor Progression and Therapy Response
AbstractIn most tumors, cancer cells show the ability to dynamically transit from a non-cancer stem-like cell to a cancer stem-like cell (CSC) state and vice versa. This cell plasticity has been associated with the epithelial-to-mesenchymal transition program (EMT) and can be regulated by tumor cell-intrinsic mechanisms and complex interactions with various tumor microenvironment (TME) components. These interactions favor the generation of a specific “CSC niche” that helps maintain the main properties, phenotypic plasticity and metastatic potential of this subset of tumor cells. For this reason, TME has been recognized...
Source: Cancer Microenvironment - October 2, 2019 Category: Cancer & Oncology Source Type: research

Kinins in Glioblastoma Microenvironment
AbstractTumour progression involves interactions among various cancer cell clones, including the cancer stem cell subpopulation and exogenous cellular components, termed cancer stromal cells. The latter include a plethora of tumour infiltrating immunocompetent cells, among which are also immuno-modulatory mesenchymal stem cells, which by vigorous migration to growing tumours and susequent transdifferentiation into various types of tumour-residing stromal cells, may either inhibit or support tumour progression. In the light of the scarce therapeutic options existing for the most malignant brain tumour glioblastoma, mesenchy...
Source: Cancer Microenvironment - August 15, 2019 Category: Cancer & Oncology Source Type: research

Pleiotropic Effects of Epithelial Mesenchymal Crosstalk on Head and Neck Cancer: EMT and beyond
In this study we analysed the effects of EMC on head and neck cancer cells. In tumor cell lines EMC was induced using media conditioned from a mix-culture of cancer cells and fibroblasts. Cell proliferation and chemotherapy response were assessed using direct cell counting . Flow cytometry, immunohistochemistry of markers of epithelial-mesenchymal transition (EMT) and subsequent TissueFaxs™ acquisition and quantification and western blot analysis were performed. Holotomographic microscopy imaging was used to visualize the effects of EMC on Cisplatin response of SCC- 25 cells. EMC induced a hybrid epithelial-mesenchymal p...
Source: Cancer Microenvironment - July 10, 2019 Category: Cancer & Oncology Source Type: research

Ascites from Ovarian Cancer Induces Novel Fucosylated Proteins
AbstractOvarian cancer is considered to be the most lethal type of gynecological cancer. During the advanced stages of ovarian cancer, an accumulation of ascites is observed. Fucosylation has been classified as an abnormal post-translational modification that is present in many diseases, including ovarian cancer. Ovarian cancer cells that are cultured with ascites stimulation change their morphology; concomitantly, the fucosylation process is altered. However, it is not known which fucosylated proteins are modified. The goal of this work was to identify the differentially fucosylated proteins that are expressed by ovarian ...
Source: Cancer Microenvironment - July 1, 2019 Category: Cancer & Oncology Source Type: research

Pyruvate Kinase M2: a Metabolic Bug in Re-Wiring the Tumor Microenvironment
AbstractMetabolic reprogramming is a newly emerged hallmark of cancer attaining a recent consideration as an essential factor for the progression and endurance of cancer cells. A prime event of this altered metabolism is increased glucose uptake and discharge of lactate into the cells surrounding constructing a favorable tumor niche. Several oncogenic factors help in promoting this consequence including, pyruvate kinase M2 (PKM2) a rate-limiting enzyme of glycolysis in tumor metabolism via exhibiting its low pyruvate kinase activity and nuclear moon-lightening functions to increase the synthesis of lactate and macromolecul...
Source: Cancer Microenvironment - June 9, 2019 Category: Cancer & Oncology Source Type: research

Immunosuppressive Tumor Microenvironment Status and Histological Grading of Endometrial Carcinoma
This study highlights significant differences in the EC intergrades immune status especially the tumor-infiltrating c ell types and their activation status as well as in the molecular factors produced by the environment. The immune microenvironment of grade 1 ECs hints at a robust tumoricidal milieu while that of higher grades is more evocative of a tolerogenic milieu. This genes-based immunological monitoring of t umors that easily highlights significant intergrade differences relating to the density, composition and functional state of the leukocyte infiltrate, could give solid arguments for choosing the best therapeutic...
Source: Cancer Microenvironment - May 26, 2019 Category: Cancer & Oncology Source Type: research

Targeting Hyaluronan Interactions for Glioblastoma Stem Cell Therapy
AbstractEven with rigorous treatments, glioblastoma multiforme (GBM) has an abysmal median survival rate, greatly due to the drug-resistant glioblastoma stem cell (GSC) population. GSCs are known to remodel their microenvironment, but the precise role of extracellular matrix components hyaluronic acid (HA) and hyaluronidases (HAases) on the GSC population is still largely unknown. Our objective was to determine how HAase can sensitize GSCs to chemotherapy drugs by disrupting the HA-CD44 signaling. GBM cell line U87-MG and patient-derived D456 cells were grown in GSC-enriching media and treated with HA or HAase. Expressions...
Source: Cancer Microenvironment - May 10, 2019 Category: Cancer & Oncology Source Type: research

Cancer-Associated Fibroblasts Enhance Survival and Progression of the Aggressive Pancreatic Tumor Via FGF-2 and CXCL8
AbstractPancreatic ductal adenocarcinoma remains one of the most challenging human cancers. Desmoplasia is predominant in this disease exhibiting a strong stromal reaction with an abundance of the cancer-associated fibroblasts (CAFs). We aimed in this study to investigate the reciprocal interaction between the tumor cells and the CAFs and its effect on tumor cells survival. We hypothesized that the survival of pancreatic cancer cell with aggressive phenotype is modulated by the Interactions between malignant pancreatic tumor cells and surrounding CAFs. To examine this, we utilized co-culture methods where tumor cells with ...
Source: Cancer Microenvironment - April 25, 2019 Category: Cancer & Oncology Source Type: research

Mechanobiology of Cancer Stem Cells and Their Niche
AbstractThough the existence of cancer stem cells remained enigmatic initially, over the time their participation in tumorigenesis and tumor progression has become highly evident. Today, they are also appreciated as the causal element for tumor heterogeneity and drug-resistance. Cancer stem cells activate a set of molecular pathways some of which are triggered by the unique mechanical properties of the tumor tissue stroma. A relatively new field called mechanobiology has emerged, which aims to critically evaluate the mechanical properties associated with biological events like tissue morphogenesis, cell-cell or cell-matrix...
Source: Cancer Microenvironment - April 18, 2019 Category: Cancer & Oncology Source Type: research

Altered T Cell Migratory Capacity in the Progression from Barrett Oesophagus to Oesophageal Adenocarcinoma
This study examined the chemokine networks governing T cell migration to oesophageal tissue during disease progression. Here, we have identified that circulating T cells in OAC patients, exhibit impaired migratory capacity with decreased frequencies of Th1-associated CXCR3+ and Th17-associated CCR6+ cells. Despite the abundance of Th1 chemokines RANTES (CCL5) and MIP-1 α (CCL3) in OAC tumour, enrichments of intratumoural T cells expressing corresponding receptors were not observed. These data suggest that T cell infiltration of oesophageal tissue is compromised in OAC and suggest that future therapies targeting T cell tra...
Source: Cancer Microenvironment - March 3, 2019 Category: Cancer & Oncology Source Type: research

Editorial Comment: Deciphering the “Metastasome” Leads to Novel Hypotheses on Understanding the Evolution of Metastasis and Implicates Consequences for Metastasis Therapy and Prevention
(Source: Cancer Microenvironment)
Source: Cancer Microenvironment - February 27, 2019 Category: Cancer & Oncology Source Type: research

The Tumor Microenvironment in Post-Transplant Lymphoproliferative Disorders
AbstractPost-transplant lymphoproliferative disorders (PTLDs) cover a broad spectrum of lymphoproliferative lesions arising after solid organ or allogeneic hematopoietic stem cell transplantation. The composition and function of the tumor microenvironment (TME), consisting of all non-malignant constituents of a tumor, is greatly impacted in PTLD through a complex interplay between 4 factors: 1) the graft organ causes immune stimulation through chronic antigen presentation; 2) the therapy to prevent organ rejection interferes with the immune system; 3) the oncogenic Epstein-Barr virus (EBV), present in 80% of PTLDs, has a c...
Source: Cancer Microenvironment - January 24, 2019 Category: Cancer & Oncology Source Type: research