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Tumour microenvironment

Janine Mayra da Silva, Tálita Pollyanna Moreira Dos Santos, Adriana Machado Saraiva, Ana Laura Fernandes de Oliveira, Gustavo Pompermaier Garlet, Aline Carvalho Batista, Ricardo Alves de Mesquita, Remo Castro Russo, Tarcília Aparecida da Silva
BACKGROUND: Chemokines and chemokine receptors are critical in oral tumourigenesis. The atypical chemokine receptor ACKR2 is a scavenger of CC chemokines controlling the availability of these molecules at tumour sites, but the role of ACKR2 in the context of oral carcinogenesis is unexplored. METHODS: In this study, wild-type (WT) and ACKR2 deficient mice (ACKR2-/- ) were treated with chemical carcinogen 4-nitroquinoline-1-oxide (4NQO) for induction of oral carcinogenesis...
March 14, 2018: Cytokine
J Durgan, O Florey
Entosis is a form of epithelial cell engulfment and cannibalism prevalent in human cancer. Until recently, the only known trigger for entosis was loss of attachment to the extracellular matrix, as often occurs in the tumour microenvironment. However, two new studies now reveal that entosis can also occur among adherent epithelial cells, induced by mitosis or glucose starvation. Together, these findings point to the intriguing notion that certain hallmark properties of cancer cells, including anchorage independence, aberrant proliferation and metabolic stress, can converge on the induction of cell cannibalism, a phenomenon so frequently observed in tumours...
March 13, 2018: Biochimica et Biophysica Acta
Zsofia Miskolczi, Michael P Smith, Emily J Rowling, Jennifer Ferguson, Jorge Barriuso, Claudia Wellbrock
Despite the general focus on an invasive and de-differentiated phenotype as main driver of cancer metastasis, in melanoma patients many metastatic lesions display a high degree of pigmentation, indicative for a differentiated phenotype. Indeed, studies in mice and fish show that melanoma cells switch to a differentiated phenotype at secondary sites, possibly because in melanoma differentiation is closely linked to proliferation through the lineage-specific transcriptional master regulator MITF. Importantly, while a lot of effort has gone into identifying factors that induce the de-differentiated/invasive phenotype, it is not well understood how the switch to the differentiated/proliferative phenotype is controlled...
March 16, 2018: Oncogene
Monica M Olcina, Ryan K Kim, Stavros Melemenidis, Edward E Graves, Amato J Giaccia
The complement system is an innate immune pathway typically thought of as part of the first line of defence against "non-self" species. In the context of cancer, complement has been described to have an active role in facilitating cancer-associated processes such as increased proliferation, angiogenesis and migration. Several cellular members of the tumour microenvironment express and/or produce complement proteins locally, including tumour cells. Dysregulation of the complement system has been reported in numerous tumours and increased expression of complement activation fragments in cancer patient specimens correlates with poor patient prognosis...
March 15, 2018: British Journal of Radiology
John R Apps, Gabriela Carreno, Jose Mario Gonzalez-Meljem, Scott Haston, Romain Guiho, Julie E Cooper, Saba Manshaei, Nital Jani, Annett Hölsken, Benedetta Pettorini, Robert J Beynon, Deborah M Simpson, Helen C Fraser, Ying Hong, Shirleen Hallang, Thomas J Stone, Alex Virasami, Andrew M Donson, David Jones, Kristian Aquilina, Helen Spoudeas, Abhijit R Joshi, Richard Grundy, Lisa C D Storer, Márta Korbonits, David A Hilton, Kyoko Tossell, Selvam Thavaraj, Mark A Ungless, Jesus Gil, Rolf Buslei, Todd Hankinson, Darren Hargrave, Colin Goding, Cynthia L Andoniadou, Paul Brogan, Thomas S Jacques, Hywel J Williams, Juan Pedro Martinez-Barbera
Adamantinomatous craniopharyngiomas (ACPs) are clinically challenging tumours, the majority of which have activating mutations in CTNNB1. They are histologically complex, showing cystic and solid components, the latter comprised of different morphological cell types (e.g. β-catenin-accumulating cluster cells and palisading epithelium), surrounded by a florid glial reaction with immune cells. Here, we have carried out RNA sequencing on 18 ACP samples and integrated these data with an existing ACP transcriptomic dataset...
March 14, 2018: Acta Neuropathologica
Flore-Anne Poujade, Aarren Mannion, Nicholas Brittain, Andrew Theodosi, Ellie Beeby, Katarzyna B Leszczynska, Ester M Hammond, John Greenman, Christopher Cawthorne, Isabel M Pires
BACKGROUND: Metastatic spread is responsible for the majority of cancer-associated deaths. The tumour microenvironment, including hypoxia, is a major driver of metastasis. The aim of this study was to investigate the role of the E3 ligase WSB-1 in breast cancer biology in the context of the hypoxic tumour microenvironment, particularly regarding metastatic spread. METHODS: In this study, WSB-1 expression was evaluated in breast cancer cell lines and patient samples...
March 15, 2018: British Journal of Cancer
Song Xu, Kim De Veirman, Ann De Becker, Karin Vanderkerken, Ivan Van Riet
Multiple myeloma (MM) is a malignant plasma cell (PC) disorder, characterized by a complex interactive network of tumour cells and the bone marrow (BM) stromal microenvironment, contributing to MM cell survival, proliferation and chemoresistance. Mesenchymal stem cells (MSCs) represent the predominant stem cell population of the bone marrow stroma, capable of differentiating into multiple cell lineages, including fibroblasts, adipocytes, chondrocytes and osteoblasts. MSCs can migrate towards primary tumours and metastatic sites, implying that these cells might modulate tumour growth and metastasis...
February 22, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Luisa Bonilla, Amit Oza, Stephanie Lheureux
Epithelial Ovarian Cancer (EOC) is the most lethal gynecological malignancy. EOC outcomes remain unsatisfactory despite aggressive surgical approach, disease chemo-sensitivity and recent introduction of agents targeting angiogenesis and tumour genome instability. Advances in EOC research have allowed for a tailored treatment approach and accelerated development of novel treatments strategies from bench to bed side, anticipated to improve patient outcomes. Areas covered: Comprehensive review of growth factor receptor antagonists for EOC treatment currently in different stages of development was performed...
March 2018: Expert Opinion on Emerging Drugs
Dai Fukumura, Jonas Kloepper, Zohreh Amoozgar, Dan G Duda, Rakesh K Jain
Immunotherapy has emerged as a major therapeutic modality in oncology. Currently, however, the majority of patients with cancer do not derive benefit from these treatments. Vascular abnormalities are a hallmark of most solid tumours and facilitate immune evasion. These abnormalities stem from elevated levels of proangiogenic factors, such as VEGF and angiopoietin 2 (ANG2); judicious use of drugs targeting these molecules can improve therapeutic responsiveness, partially owing to normalization of the abnormal tumour vasculature that can, in turn, increase the infiltration of immune effector cells into tumours and convert the intrinsically immunosuppressive tumour microenvironment (TME) to an immunosupportive one...
March 6, 2018: Nature Reviews. Clinical Oncology
H Ballestero Fêo, L Montoya Flórez, R S Yamatogi, A Prado Duzanski, J P Araújo, R A Oliveira, N S Rocha
The canine transmissible venereal tumour (CTVT) is a transmissible cancer that is spread naturally between dogs, with the ability to develop and evade the immune system, despite strict immune surveillance of the host. Furthermore, molecular signalling between cells of the immune system and the tumour microenvironment appear to influence the behaviour and development of the tumour. Thus, this study aimed to quantify the expression of genes related to the immune system such as IL-6, IFN-γ, and TGF-β, as well as angiogenic factors (VEGF, CXCR4), in CTVT cells in vivo and in vitro (primary culture), correlating with the clinical response of the animals treated with vincristine...
March 5, 2018: Veterinary and Comparative Oncology
Han Qiao, Tingting Tang
Cancer metastasis to bone is a three-dimensional (3D), multistep, dynamic process that requires the sequential involvement of three microenvironments, namely, the primary tumour microenvironment, the circulation microenvironment and the bone microenvironment. Engineered 3D approaches allow for a vivid recapitulation of in vivo cancerous microenvironments in vitro, in which the biological behaviours of cancer cells can be assessed under different metastatic conditions. Therefore, modelling bone metastasis microenvironments with 3D cultures is imperative for advancing cancer research and anti-cancer treatment strategies...
2018: Bone Research
Matthew A Lakins, Ehsan Ghorani, Hafsa Munir, Carla P Martins, Jacqueline D Shields
Tumours have developed strategies to interfere with most steps required for anti-tumour immune responses. Although many populations contribute to anti-tumour responses, tumour-infiltrating cytotoxic T cells dominate, hence, many suppressive strategies act to inhibit these. Tumour-associated T cells are frequently restricted to stromal zones rather than tumour islands, raising the possibility that the tumour microenvironment, where crosstalk between malignant and "normal" stromal cells exists, may be critical for T cell suppression...
March 5, 2018: Nature Communications
Ain Zubaidah Ayob, Thamil Selvee Ramasamy
BACKGROUND: Cancer stem cells (CSCs) are subpopulations of cancer cells sharing similar characteristics as normal stem or progenitor cells such as self-renewal ability and multi-lineage differentiation to drive tumour growth and heterogeneity. Throughout the cancer progression, CSC can further be induced from differentiated cancer cells via the adaptation and cross-talks with the tumour microenvironment as well as a response from therapeutic pressures, therefore contributes to their heterogeneous phenotypes...
March 6, 2018: Journal of Biomedical Science
G E Melling, S E Flannery, S A Abidin, H Clemmens, P Prajapati, E E Hinsley, S Hunt, J W F Catto, R D Coletta, M Mellone, G J Thomas, E K Parkinson, S S Prime, I C Paterson, D J Buttle, D W Lambert
The dissemination of cancer cells to local and distant sites depends on a complex and poorly understood interplay between malignant cells and the cellular and non-cellular components surrounding them, collectively termed the tumour microenvironment. One of the most abundant cell types of the tumour microenvironment is the fibroblast, which becomes corrupted by locally derived cues such as TGF-β1 and acquires an altered, heterogeneous phenotype (cancer-associated fibroblast, CAF) supportive of tumour cell invasion and metastasis...
February 28, 2018: Carcinogenesis
Niken M Mahaweni, Gerard M J Bos, Constantine S Mitsiades, Marcel G J Tilanus, Lotte Wieten
Natural killer (NK) cell-based immunotherapy is a promising novel approach to treat cancer. However, NK cell function has been shown to be potentially diminished by factors common in the tumor microenvironment (TME). In this study, we assessed the synergistic potential of antibody-dependent cell-mediated cytotoxicity (ADCC) and killer immunoglobin-like receptor (KIR)-ligand mismatched NK cells to potentiate NK cell antitumor reactivity in multiple myeloma (MM). Hypoxia, lactate, prostaglandin E2 (PGE2) or combinations were selected to mimic the TME...
March 2, 2018: Cancer Immunology, Immunotherapy: CII
Eroje M Ahmed, Gagori Bandopadhyay, Beth Coyle, Anna Grabowska
PURPOSE: Glioblastoma (GBM) is the commonest brain tumour in adults. A sub-population of cells within these tumours, known as cancer stem cells (CSCs), is thought to mediate their chemo-/radiotherapy resistance. CD133 is a cell surface marker that is used to identify and isolate GBM CSCs. However, its functional significance, as well as the relevant microenvironment in which to study CD133, have so far remained unknown. Here, we examined the effect of hypoxia on the expression of CD133 and on that of the hypoxia-related factors HIF-1α and HIF-2α, and the potential functional significance of CD133 expression on the acquisition of chemo-resistance by GBM cells...
February 28, 2018: Cellular Oncology (Dordrecht)
Jun Cao, Haoran Zheng, Rui Hu, Jianhong Liao, Zengming Fei, Xuan Wei, Xiong Xiong, Fanglin Zhang, Hua Zheng, Dan Li
The drug controlled release responding to tumour microenvironment is a hotspot for cancer therapy research. Herein, pH-sensitive shell-core nanoparticles (NPs) were devised and fabricated for tumour treatment. The detailed characterisations of their structures demonstrated the successful formation of the precursors and NPs. More importantly, the NPs show excellent features, i.e., negative surface potential, narrow size distribution, and suitable dimension for cell penetration. And they have superior stability in pH 7...
December 1, 2017: Journal of Biomedical Nanotechnology
Miki Young, Darren Rodenhizer, Teresa Dean, Elisa D'Arcangelo, Bin Xu, Laurie Ailles, Alison P McGuigan
Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment and have been shown to play an important role in the progression of cancer. To probe these tumour-stroma interactions, we incorporated CAFs derived from head and neck cancer patients and squamous carcinoma cells of the hypopharynx (FaDu) into the Tissue Roll for the Analysis of Cellular Environment and Response (TRACER) platform to establish a co-culture platform that simulates the CAF-tumour microenvironmental interactions in head and neck tumours...
February 19, 2018: Biomaterials
Thomas D Lewin, Philip K Maini, Eduardo G Moros, Heiko Enderling, Helen M Byrne
Current protocols for delivering radiotherapy are based primarily on tumour stage and nodal and metastases status, even though it is well known that tumours and their microenvironments are highly heterogeneous. It is well established that the local oxygen tension plays an important role in radiation-induced cell death, with hypoxic tumour regions responding poorly to irradiation. Therefore, to improve radiation response, it is important to understand more fully the spatiotemporal distribution of oxygen within a growing tumour before and during fractionated radiation...
February 27, 2018: Bulletin of Mathematical Biology
Ting Jiang, Bo Zhang, Long Zhang, Xuemei Wu, Haichun Li, Shun Shen, Zimiao Luo, Xianping Liu, Yu Hu, Zhiqing Pang, Xinguo Jiang
The unique tumour microenvironment (TM) of pancreatic ductal adenocarcinoma (PDA) including highly desmoplastic ECM and low tumour perfusion supports a considerable barrier for effective delivery of nanomedicines. Effectively modulating PDA microenvironment to enhance tumour drug delivery represents a pinpoint in the field of PDA treatment. In this study, it was the first time that biomimetic nanoparticles, which were designed in the form of erythrocyte membrane-camouflaged PLGA nanoparticles (MNP), were utilized for PDA microenvironment modulation...
February 27, 2018: Artificial Cells, Nanomedicine, and Biotechnology
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