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Tumour microenvironment

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https://www.readbyqxmd.com/read/28210916/a-multiscale-mathematical-model-of-tumour-invasive-growth
#1
Lu Peng, Dumitru Trucu, Ping Lin, Alastair Thompson, Mark A J Chaplain
Known as one of the hallmarks of cancer (Hanahan and Weinberg in Cell 100:57-70, 2000) cancer cell invasion of human body tissue is a complicated spatio-temporal multiscale process which enables a localised solid tumour to transform into a systemic, metastatic and fatal disease. This process explores and takes advantage of the reciprocal relation that solid tumours establish with the extracellular matrix (ECM) components and other multiple distinct cell types from the surrounding microenvironment. Through the secretion of various proteolytic enzymes such as matrix metalloproteinases or the urokinase plasminogen activator (uPA), the cancer cell population alters the configuration of the surrounding ECM composition and overcomes the physical barriers to ultimately achieve local cancer spread into the surrounding tissue...
February 16, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28210073/macrophages-as-key-drivers-of-cancer-progression-and-metastasis
#2
REVIEW
Sebastian R Nielsen, Michael C Schmid
Macrophages are one of the most abundant immune cells in the tumour microenvironment of solid tumours and their presence correlates with reduced survival in most cancers. Macrophages are present at all stages of tumour progression and stimulate angiogenesis, tumour cell invasion, and intravasation at the primary site. At the metastatic site, macrophages and monocytes prepare for the arrival of disseminated tumour cells and promote their extravasation and survival by inhibiting immune-mediated clearance or by directly engaging with tumour cells to activate prosurvival signalling pathways...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28205552/a-class-of-extracellular-vesicles-from-breast-cancer-cells-activates-vegf-receptors-and-tumour-angiogenesis
#3
Qiyu Feng, Chengliang Zhang, David Lum, Joseph E Druso, Bryant Blank, Kristin F Wilson, Alana Welm, Marc A Antonyak, Richard A Cerione
Non-classical secretory vesicles, collectively referred to as extracellular vesicles (EVs), have been implicated in different aspects of cancer cell survival and metastasis. Here, we describe how a specific class of EVs, called microvesicles (MVs), activates VEGF receptors and tumour angiogenesis through a unique 90 kDa form of VEGF (VEGF90K). We show that VEGF90K is generated by the crosslinking of VEGF165, catalysed by the enzyme tissue transglutaminase, and associates with MVs through its interaction with the chaperone Hsp90...
February 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28198360/secreted-clic3-drives-cancer-progression-through-its-glutathione-dependent-oxidoreductase-activity
#4
Juan R Hernandez-Fernaud, Elena Ruengeler, Andrea Casazza, Lisa J Neilson, Ellie Pulleine, Alice Santi, Shehab Ismail, Sergio Lilla, Sandeep Dhayade, Iain R MacPherson, Iain McNeish, Darren Ennis, Hala Ali, Fernanda G Kugeratski, Heba Al Khamici, Maartje van den Biggelaar, Peter V E van den Berghe, Catherine Cloix, Laura McDonald, David Millan, Aoisha Hoyle, Anna Kuchnio, Peter Carmeliet, Stella M Valenzuela, Karen Blyth, Huabing Yin, Massimiliano Mazzone, Jim C Norman, Sara Zanivan
The secretome of cancer and stromal cells generates a microenvironment that contributes to tumour cell invasion and angiogenesis. Here we compare the secretome of human mammary normal and cancer-associated fibroblasts (CAFs). We discover that the chloride intracellular channel protein 3 (CLIC3) is an abundant component of the CAF secretome. Secreted CLIC3 promotes invasive behaviour of endothelial cells to drive angiogenesis and increases invasiveness of cancer cells both in vivo and in 3D cell culture models, and this requires active transglutaminase-2 (TGM2)...
February 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28187910/analysis-of-gap-junctional-intercellular-communications-using-a-dielectrophoresis-based-microchip
#5
Marta Tellez-Gabriel, Céline Charrier, Bénédicte Brounais-Le Royer, Mathilde Mullard, Hannah K Brown, Franck Verrecchia, Dominique Heymann
Gap junctions are transmembrane structures that directly connect the cytoplasm of adjacent cells, making intercellular communications possible. It has been shown that the behaviour of several tumours - such as bone tumours - is related to gap junction intercellular communications (GJIC). Several methodologies are available for studying GJIC, based on measuring different parameters that are useful for multiple applications, such as the study of carcinogenesis for example. These methods nevertheless have several limitations...
February 6, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28186876/automated-classification-of-breast-cancer-stroma-maturity-from-histological-images
#6
Sara Reis, Patrycja Gazinska, John Hipwell, Thomy Mertzanidou, Kalnisha Naidoo, Norman Williams, Sarah Pinder, David J Hawkes
OBJECTIVE: The tumour microenvironment plays a crucial role in regulating tumour progression by a number of different mechanisms, in particular the remodelling of collagen fibres in tumour-associated stroma, which has been reported to be related to patient survival. The underlying motivation of this work is that remodelling of collagen fibres gives rise to observable patterns in Hematoxylin and Eosin (H&E) stained slides from clinical cases of invasive breast carcinoma that the pathologist can label as mature or immature stroma...
February 7, 2017: IEEE Transactions on Bio-medical Engineering
https://www.readbyqxmd.com/read/28181494/microenvironment-derived-factors-driving-metastatic-plasticity-in-melanoma
#7
Isabella S Kim, Silja Heilmann, Emily R Kansler, Yan Zhang, Milena Zimmer, Kajan Ratnakumar, Robert L Bowman, Theresa Simon-Vermot, Myles Fennell, Ralph Garippa, Liang Lu, William Lee, Travis Hollmann, Joao B Xavier, Richard M White
Cellular plasticity is a state in which cancer cells exist along a reversible phenotypic spectrum, and underlies key traits such as drug resistance and metastasis. Melanoma plasticity is linked to phenotype switching, where the microenvironment induces switches between invasive/MITF(LO) versus proliferative/MITF(HI) states. Since MITF also induces pigmentation, we hypothesize that macrometastatic success should be favoured by microenvironments that induce a MITF(HI)/differentiated/proliferative state. Zebrafish imaging demonstrates that after extravasation, melanoma cells become pigmented and enact a gene expression program of melanocyte differentiation...
February 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28176852/a-critical-role-of-platelet-tgf-%C3%AE-release-in-podoplanin-mediated-tumour-invasion-and-metastasis
#8
Ai Takemoto, Mina Okitaka, Satoshi Takagi, Miho Takami, Shigeo Sato, Makoto Nishio, Sakae Okumura, Naoya Fujita
The tumour microenvironment is critical for various characteristics of tumour malignancies. Platelets, as part of the tumour microenvironment, are associated with metastasis formation via increasing the rate of tumour embolus formation in microvasculature. However, the mechanisms underlying the ability of tumour cells to acquire invasiveness and extravasate into target organs at the site of embolization remain unclear. In this study, we reported that platelet aggregation-inducing factor podoplanin expressed on tumour cell surfaces were found to not only promote the formation of tumour-platelet aggregates via interaction with platelets, but also induced the epithelial-mesenchymal transition (EMT) of tumour cells by enhancing transforming growth factor-β (TGF-β) release from platelets...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28176769/heterogeneity-of-macrophage-infiltration-and-therapeutic-response-in-lung-carcinoma-revealed-by-3d-organ-imaging
#9
Michael F Cuccarese, J Matthew Dubach, Christina Pfirschke, Camilla Engblom, Christopher Garris, Miles A Miller, Mikael J Pittet, Ralph Weissleder
Involvement of the immune system in tumour progression is at the forefront of cancer research. Analysis of the tumour immune microenvironment has yielded a wealth of information on tumour biology, and alterations in some immune subtypes, such as tumour-associated macrophages (TAM), can be strong prognostic indicators. Here, we use optical tissue clearing and a TAM-targeting injectable fluorescent nanoparticle (NP) to examine three-dimensional TAM composition, tumour-to-tumour heterogeneity, response to colony-stimulating factor 1 receptor (CSF-1R) blockade and nanoparticle-based drug delivery in murine pulmonary carcinoma...
February 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28176650/is-there-a-role-for-epigenetic-enhancement-of-immunomodulatory-approaches-to-cancer-treatment
#10
Kirsty J Flower, Sadaf Ghaem-Maghami, Robert Brown
The efficacy of cancer immunotherapy relies on the ability of the host immune system to recognise the cancer as non-self and eliminate it from the body. Whilst this is an extremely fertile area of medical research, with positive clinical trials showing durable responses, attention must be paid to the subset of patients that do not respond to these treatments. Immune surveillance and immunoediting by the host could itself select for immune-evasive tumour cells during tumour development leading to immunotherapy resistance...
February 5, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28176648/oncolytic-viruses-the-best-is-yet-to-come
#11
Chantal G Lemay, Brian A Keller, Robert E Edge, Masato Abei, John C Bell
Oncolytic viruses are a promising anti-cancer platform, achieving significant pre-clinical and clinical milestones in recent years. A full arsenal of selective, safe, and effective viruses has been developed with some emerging pre-clinical research focusing on optimizing these therapies in the face of remaining challenges, both in the bloodstream and in the tumour microenvironment. Herein we discuss the recent progress in pre-clinical virotherapy research to address these challenges, with special focus on innovative strategies that seek to complement the current strengths of virotherapy, ensuring an optimal multi-faceted attack on cancer...
February 6, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28174027/forkhead-box-p3-regulatory-t-cells-and-toll-like-receptor-2-co-expression-in-oral-squamous-cell-carcinoma
#12
H M Hussaini, V P B Parachuru, G J Seymour, A M Rich
BACKGROUND: The function of forkhead box-P3 (FoxP3) regulatory T cells (Treg) and toll-like receptor (TLR)2 protein in the oral cancer microenvironment is not fully understood, but evidence from other malignancies suggests it is likely they are involved with tumour development and progression. The aim of this study was to investigate the distribution of FoxP3(+)cells, TLR2(+) cells and double-labelled FoxP3(+)TLR2(+) immune cells in oral squamous cell carcinoma (OSCC), using immunohistochemistry (IHC) and immunofluorescence (IF)...
February 4, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28174005/the-expression-of-cancer-stem-cell-markers-in-human-colorectal-carcinoma-cells-in-a-microenvironment-dependent-manner
#13
Vaidotas Stankevicius, Linas Kunigenas, Edvinas Stankunas, Karolina Kuodyte, Egle Strainiene, Jonas Cicenas, Narimantas E Samalavicius, Kestutis Suziedelis
Numerous lines of evidence support the hierarchical model of cancer development and tumor initiation. According to the theory, cancer stem cells play a crucial role in the formation of the tumor and should be targeted for more effective anticancer treatment. However, cancer stem cells quickly loose their characteristics when propagated as 2D cell culture, indicating that the 2D cell culture does not provide the appropriate settings to maintain an in vivo environment. In this study we have investigated the expression of self-renewal, cancer stem cell and epithelial to mesenchymal transition markers after the transfer of human colorectal carcinoma cell DLD1 and HT29 lines from 2D cell cultures to scaffold-attached laminin rich extracellular matrix and scaffold-free multicellular spheroid 3D culture models...
February 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28173828/cancer-cells-increase-endothelial-cell-tube-formation-and-survival-by-activating-the-pi3k-akt-signalling-pathway
#14
Hao-Wei Cheng, Yi-Fang Chen, Jau-Min Wong, Chia-Wei Weng, Hsuan-Yu Chen, Sung-Liang Yu, Huei-Wen Chen, Ang Yuan, Jeremy J W Chen
BACKGROUND: Angiogenesis is a hallmark of cancer and plays a critical role in lung cancer progression, which involves interactions between cancer cells, endothelial cells and the surrounding microenvironment. However, the gene expression profiles and the changes in the biological phenotype of vascular endothelial cells after interactions with lung cancer cells remain unclear. METHODS: An indirect transwell co-culture system was used to survey the interaction between human umbilical vein endothelial cells (HUVECs) and human lung adenocarcinoma CL1-5 cells, as well as to investigate the morphological and molecular changes of HUVECs...
February 7, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28166195/detecting-intratumoral-heterogeneity-of-egfr-activity-by-liposome-based-in-vivo-transfection-of-a-fluorescent-biosensor
#15
G Weitsman, N J Mitchell, R Evans, A Cheung, T L Kalber, R Bofinger, G O Fruhwirth, M Keppler, Z V F Wright, P R Barber, P Gordon, T de Koning, W Wulaningsih, K Sander, B Vojnovic, S Ameer-Beg, M Lythgoe, J N Arnold, E Årstad, F Festy, H C Hailes, A B Tabor, T Ng
Despite decades of research in the epidermal growth factor receptor (EGFR) signalling field, and many targeted anti-cancer drugs that have been tested clinically, the success rate for these agents in the clinic is low, particularly in terms of the improvement of overall survival. Intratumoral heterogeneity is proposed as a major mechanism underlying treatment failure of these molecule-targeted agents. Here we highlight the application of fluorescence lifetime microscopy (FLIM)-based biosensing to demonstrate intratumoral heterogeneity of EGFR activity...
February 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28165633/back-to-the-future-routine-morphological-assessment-of-the-tumour-microenvironment-is-prognostic-in-stage-ii-iii-colon-cancer-in-a-large-population-based-study
#16
Seán O Hynes, Helen G Coleman, Paul J Kelly, Steven Irwin, Roisin F O'Neill, Ronan T Gray, Claire McGready, Philip D Dunne, Stephen McQuaid, Jacqueline A James, Manuel Salto-Tellez, Maurice B Loughrey
AIMS: Both morphological and molecular approaches have highlighted the biological and prognostic importance of the tumour microenvironment in colorectal cancer (CRC). Despite this, microscopic assessment of tumour microenvironment has not been adopted into routine practice. METHODS AND RESULTS: Based on existing evidence, we selected specific morphological features relating to peritumoral inflammatory and stromal responses, agreed criteria for scoring, and assessed these in representative H&E-stained whole tumour sections, from a population-based cohort of 445 stage II/III colon cancer cases...
February 6, 2017: Histopathology
https://www.readbyqxmd.com/read/28163102/the-peritumoural-adipose-tissue-microenvironment-and-cancer-the-roles-of-fatty-acid-binding-protein-4-and-fatty-acid-binding-protein-5
#17
S Guaita-Esteruelas, J Gumà, L Masana, J Borràs
The adipose tissue microenvironment plays a key role in tumour initiation and progression because it provides fatty acids and adipokines to tumour cells. The fatty acid-binding protein (FABP) family is a group of small proteins that act as intracellular fatty acid transporters. Adipose-derived FABPs include FABP4 and FABP5. Both have an important role in lipid-related metabolic processes and overexpressed in many cancers, such as breast, prostate, colorectal and ovarian. Moreover, their expression in peritumoural adipose tissue is deregulated, and their circulating levels are upregulated in some tumours...
February 2, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28155728/multi-scale-mathematical-modelling-of-tumour-growth-and-microenvironments-in-anti-angiogenic-therapy
#18
Yan Cai, Jie Zhang, Zhiyong Li
BACKGROUND: Angiogenesis, a process of generation of new blood vessels from the pre-existing vasculature, has been demonstrated to be a basic prerequisite for sustainable growth and proliferation of tumour. Anti-angiogenic treatments show normalization of tumour vasculature and microenvironment at least transiently in both preclinical and clinical settings. METHODS: In this study, we proposed a multi-scale mathematical model to simulate the dynamic changes of tumour microvasculature and microenvironment in response to anti-angiogenic drug endostatin (ES)...
December 28, 2016: Biomedical Engineering Online
https://www.readbyqxmd.com/read/28155598/development-of-in-vitro-co-culture-model-in-anti-cancer-drug-development-cascade
#19
Ruiling Xu
Tumour microenvironment is recognized as a major determinant of intrinsic resistance to anticancer therapies. In solid tumour types, such as breast cancer, lung cancer and pancreatic cancer, stromal components provide a fibrotic niche, which promotes stemness, EMT, chemo- and radio-resistance of tumour. However, this microenvironment is not recapitulated in the conventional cell monoculture or xenografts, hence these in vitro and in vivo preclinical models are unlikely to be predictive of clinical response; which might attribute to the poor predictivity of these preclinical drug-screening models...
February 1, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28148268/mesenchymal-stem-cells-key-players-in-cancer-progression
#20
REVIEW
Sarah M Ridge, Francis J Sullivan, Sharon A Glynn
Tumour progression is dependent on the interaction between tumour cells and cells of the surrounding microenvironment. The tumour is a dynamic milieu consisting of various cell types such as endothelial cells, fibroblasts, cells of the immune system and mesenchymal stem cells (MSCs). MSCs are multipotent stromal cells that are known to reside in various areas such as the bone marrow, fat and dental pulp. MSCs have been found to migrate towards inflammatory sites and studies have shown that they also migrate towards and incorporate into the tumour...
February 1, 2017: Molecular Cancer
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