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tumor stromal microenvironment

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https://www.readbyqxmd.com/read/28097809/cancer-associated-fibroblasts-promote-m2-polarization-of-macrophages-in-pancreatic-ductal-adenocarcinoma
#1
Aibin Zhang, Yigang Qian, Zhou Ye, Haiyong Chen, Haiyang Xie, Lin Zhou, Yan Shen, Shusen Zheng
Pancreatic ductal adenocarcinoma (PDAC) is characterized by remarkable desmoplasia with infiltration of distinct cellular components. Cancer-associated fibroblasts (CAFs) has been shown to be among the most prominent cells and played a significant role in shaping the tumor microenvironment by interacting with other type of cells. Here, we aimed to investigate the effect of CAFs in modulating phenotype of tumor-associated macrophages (TAM). Under treatment of CAFs conditioned medium (CM) or direct co-culture with CAFs, monocytes exhibited enhanced expression of CD206 and CD163 compared with control group (P < 0...
January 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28096419/stromal-cues-regulate-the-pancreatic-cancer-epigenome-and-metabolome
#2
Mara H Sherman, Ruth T Yu, Tiffany W Tseng, Cristovao M Sousa, Sihao Liu, Morgan L Truitt, Nanhai He, Ning Ding, Christopher Liddle, Annette R Atkins, Mathias Leblanc, Eric A Collisson, John M Asara, Alec C Kimmelman, Michael Downes, Ronald M Evans
A fibroinflammatory stromal reaction cooperates with oncogenic signaling to influence pancreatic ductal adenocarcinoma (PDAC) initiation, progression, and therapeutic outcome, yet the mechanistic underpinning of this crosstalk remains poorly understood. Here we show that stromal cues elicit an adaptive response in the cancer cell including the rapid mobilization of a transcriptional network implicated in accelerated growth, along with anabolic changes of an altered metabolome. The close overlap of stroma-induced changes in vitro with those previously shown to be regulated by oncogenic Kras in vivo suggests that oncogenic Kras signaling-a hallmark and key driver of PDAC-is contingent on stromal inputs...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096238/activation-of-trpa1-channel-by-antibacterial-agent-triclosan-induces-vegf-secretion-in-human-prostate-cancer-stromal-cells
#3
Sandra Derouiche, Pascal Mariot, Marine Warnier, Eric Vancauwenberghe, Gabriel Bidaux, Pierre Gosset, Brigitte Mauroy, Jean-Louis Bonnal, Christian Slomianny, Philippe Delcourt, Etienne Dewailly, Natalia Prevarskaya, Morad Roudbaraki
Accruing evidence indicates that exposure to environmental compounds may adversely impact human health and promote carcinogenesis. Triclosan (TCS), an antimicrobial agent widely used as a preservative in personal care products, has been shown to act as an endocrine disruptor in hormone-dependent tissues. Here we demonstrate a new molecular mechanism by which TCS stimulates the secretion by human prostate cancer stromal cells of Vascular Endothelial Growth Factor (VEGF), a factor known to promote tumour growth...
January 17, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28075171/the-role-of-tumor-microenvironment-in-collective-tumor-cell-invasion
#4
Jia-Shun Wu, Su-Rui Sheng, Xin-Hua Liang, Ya-Ling Tang
For many cancer types, cancer cells invade into surrounding tissues by collective movement of cell groups that remain connected via cell-cell junctions. This migration is completely distinguished from single-cell migration, in which cancer cells disrupt the tight intercellular junctions and gain a mesenchymal phenotype. Recently, emerging evidence has revealed that collective cell invasion depends on not only cell-intrinsic mechanisms but also on extracellular mechanisms by bidirectional interplay between the tumor cell and the tumor environment...
January 11, 2017: Future Oncology
https://www.readbyqxmd.com/read/28069800/label-free-raman-spectroscopy-detects-stromal-adaptations-in-premetastatic-lungs-primed-by-breast-cancer
#5
Santosh Kumar Paidi, Asif Rizwan, Chao Zheng, Menglin Cheng, Kristine Glunde, Ishan Barman
Recent advances in animal modeling, imaging technology, and functional genomics have permitted precise molecular observations of the metastatic process. However, a comprehensive understanding of the premetastatic niche remains elusive, owing to the limited tools that can map subtle differences in molecular mediators in organ-specific microenvironments. Here, we report the ability to detect premetastatic changes in the lung microenvironment, in response to primary breast tumors, using a combination of metastatic mouse models, Raman spectroscopy, and multivariate analysis of consistent patterns in molecular expression...
January 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28067804/stromal-modulators-of-tgf-%C3%AE-in-cancer
#6
REVIEW
Brunella Costanza, Ijeoma Adaku Umelo, Justine Bellier, Vincent Castronovo, Andrei Turtoi
Transforming growth factor-β (TGF-β) is an intriguing cytokine exhibiting dual activities in malignant disease. It is an important mediator of cancer invasion, metastasis and angiogenesis, on the one hand, while it exhibits anti-tumor functions on the other hand. Elucidating the precise role of TGF-β in malignant development and progression requires a better understanding of the molecular mechanisms involved in its tumor suppressor to tumor promoter switch. One important aspect of TGF-β function is its interaction with proteins within the tumor microenvironment...
January 6, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28066687/how-little-is-too-much-how-transient-tumor-stromal-crosstalk-can-control-tumor-progression
#7
Christina H Stuelten
Tumorigenesis is driven by genetic and physiological alterations of tumor cells as well as by the host microenvironment. In a co-culture of breast cancer cells and fibroblasts, short term interactions between tumor cells and stromal fibroblasts increase levels of active, fibroblast derived TGF-β in the extracellular medium, which in turn induces an expanded metastatic pattern of MCF10CA1a cells. These findings suggest that the effects of stromal TGF-β on tumor cell phenotype can be modeled as a dynamical system rather than a continuous linear system...
October 2016: Journal of Clinical & Cellular Immunology
https://www.readbyqxmd.com/read/28062564/tgf-%C3%AE-bone-morphogenetic-protein-and-activin-signaling-and-the-tumor-microenvironment
#8
Michael W Pickup, Philip Owens, Harold L Moses
The cellular and noncellular components surrounding the tumor cells influence many aspects of tumor progression. Transforming growth factor β (TGF-β), bone morphogenetic proteins (BMPs), and activins have been shown to regulate the phenotype and functions of the microenvironment and are attractive targets to attenuate protumorigenic microenvironmental changes. Given the pleiotropic nature of the cytokines involved, a full understanding of their effects on numerous cell types in many contexts is necessary for proper clinical intervention...
January 6, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28057717/pathology-driven-comprehensive-proteomic-profiling-of-the-prostate-cancer-tumour-microenvironment
#9
Lisa Staunton, Claire Tonry, Rosina Lis, Virginia Espina, Lance Liotta, Rosanna Inziatari, Michaela Bowden, Aurelie Fabre, John O'Leary, Stephen P Finn, Massimo Loda, Stephen R Pennington
: Prostate cancer (PCa) is the second most common cancer in men worldwide. Gleason grading is an important predictor of PCa outcomes and is influential in determining patient treatment options. Clinical decisions based on a Gleason score of 7 are difficult as the prognosis for individuals diagnosed with Gleason 4+3 cancer is much worse than for those diagnosed with Gleason 3+4 cancer. Laser capture microdissection (LCM) is a highly precise method to isolate specific cell populations or discrete microregions from tissues...
January 5, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28052009/cancer-associated-fibroblasts-promote-an-immunosuppressive-microenvironment-through-the-induction-and-accumulation-of-protumoral-macrophages
#10
Hideyuki Takahashi, Koichi Sakakura, Takeshi Kudo, Minoru Toyoda, Kyoichi Kaira, Tetsunari Oyama, Kazuaki Chikamatsu
Stromal cells in the tumor microenvironment (TME) closely interact with tumor cells and affect tumor cell behavior in diverse manners. We herein investigated the mechanisms by which cancer-associated fibroblasts (CAFs) affect the functional polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC) in vitro and in human cancer samples. The expression of CD68, CD14, CD163, CD200R, CD206, HLA-G, CD80, and CD86 was higher in CD14-positive cells co-cultured with the culture supernatants of CAFs established from OSCC specimens (CAF-educated cells) than in control cells...
December 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/28043149/mesenchymal-stromal-cells-producing-tnf%C3%AE-lack-inhibitory-effect-against-a375-experimental-lung-metastasis
#11
S Tyciakova, M Matuskova, R Bohovic, L Kucerova
Cell-based anticancer therapy using mesenchymal stromal cells (MSCs) engineered to express therapeutic genes has a potential to target the cancer cells in vivo. Metastatic dissemination of melanoma remains a serious problem in the treatment. In our previous work we used MSCs overexpressing gene for tumor necrosis factor α (TNFα; MSCs/TNFα), and we achieved inhibition of melanoma xenograft growth when engineered MCSs/TNFα were coinjected with tumor cells subcutaneously. The TNFα as a pleiotropic cytokine induces apoptosis of tumor cells, creates "tumor resistant" microenvironment, enhances immune response and can have tumor destructive capacity in selected tumor types, especially in tumors of mesodermal origin...
January 3, 2017: Neoplasma
https://www.readbyqxmd.com/read/28042683/breast-tumor-stroma-a-driving-force-in-the-development-of-resistance-to-therapies
#12
REVIEW
Maryam Majidinia, Bahman Yousefi
Breast cancer is the most common cancer and the second leading cause of cancer-related death in women worldwide. In spite of huge advancements in early detection and ever-increasing knowledge of breast cancer biology, approximately 30% of patients with early-stage breast cancer experience disease recurrence. Most patients are chemosensitive and cancer free immediately after the treatment. About 50% to 70% of breast cancer patients, however, will relapse within 1 year. Such a relapse is usually concomitant with adenocarcinoma cells acquiring a chemoresistant phenotype...
January 2, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28039693/exosomal-communication-in-glioma-a-review
#13
Hongsheng Xu, Kezhong Zhang, Hailiang Zong, Ming Shang, Kai Li, Xiaoguang He
Cancer research has revealed the existence of cancer stem cells (CSCs). However, the influence of the surrounding stromal cells present in the microenvironment on CSCs is still poorly understood. The latest studies on gliomas suggested that the microenvironment of human gliomas contains both glioma stem cells (GSCs) and glioma associated (GA)-mesenchymal stem cells (MSCs; (GA-MSCs). Also, studies have suggested that nano- sized vesicles, termed exosomes, have been recently observed to contribute towards intercellular communication within the tumor niche...
November 2016: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28039358/stromal-senescence-by-prolonged-cdk4-6-inhibition-potentiates-tumor-growth
#14
Xiangnan Guan, Kyle M LaPak, Rebecca C Hennessey, Christina Y Yu, Reena Shakya, Jianying Zhang, Christin E Burd
: Senescent cells within the tumor microenvironment (TME) adopt a pro-inflammatory, senescence-associated secretory phenotype (SASP) that promotes cancer initiation, progression and therapeutic resistance. Here, exposure to Palbociclib (PD-0332991), a CDK4/6 inhibitor, induces senescence and a robust SASP in normal fibroblasts. Senescence caused by prolonged CDK4/6 inhibition is DNA damage-independent and associated with Mdm2 downregulation, whereas the SASP elicited by these cells is largely reliant upon NF-kappaB activation...
December 30, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28038471/prognostic-impact-of-immune-microenvironment-in-laryngeal-and-pharyngeal-squamous-cell-carcinoma-immune-cell-subtypes-immuno-suppressive-pathways-and-clinicopathologic-characteristics
#15
Georgia Karpathiou, Francois Casteillo, Jean-Baptiste Giroult, Fabien Forest, Pierre Fournel, Alessandra Monaya, Marios Froudarakis, Jean Marc Dumollard, Jean Michel Prades, Michel Peoc'h
BACKGROUND: Immune system affects prognosis of various malignancies. Anti-immune pathways like PD-L1 and CTLA4 are used by the tumor to overcome immune system and they serve as immunotherapy targets. The immune microenvironment of head-and-neck squamous cell carcinoma (SCCHN) has not been sufficiently studied. PATIENTS AND METHODS: 152 SCCHN were immunohistochemically studied for the expression of CD3, CD8, CD57, CD4, granzyme b, CD20, CD163, S100, PD-L1, CTLA4 and CXCR4...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28036019/lymph-nodes-and-cancer-metastasis-new-perspectives-on-the-role-of-intranodal-lymphatic-sinuses
#16
REVIEW
Rui-Cheng Ji
The lymphatic system is essential for transporting interstitial fluid, soluble antigen, and immune cells from peripheral tissues to lymph nodes (LNs). Functional integrity of LNs is dependent on intact lymphatics and effective lymph drainage. Molecular mechanisms that facilitate interactions between tumor cells and lymphatic endothelial cells (LECs) during tumor progression still remain to be identified. The cellular and molecular structures of LNs are optimized to trigger a rapid and efficient immune response, and to participate in the process of tumor metastasis by stimulating lymphangiogenesis and establishing a premetastatic niche in LNs...
December 28, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28034553/microenvironment-in-determining-chemo-resistance-in-pancreatic-cancer-neighborhood-matters
#17
REVIEW
Patricia Dauer, Alice Nomura, Ashok Saluja, Sulagna Banerjee
Every year, nearly 300,000 people are diagnosed with pancreatic cancer worldwide, and an equivalent number succumb to this disease. One of the major challenges of pancreatic cancer that contributes to its poor survival rates is the development of resistance to the standard chemotherapy. Heterogeneity of the tumor, the dense fibroblastic stroma, and the aggressive biology of the tumor all contribute to the chemoresistant phenotype. In addition, the acellular components of the tumor microenvironment like hypoxia, stress pathways in the stromal cells, and the cytokines that are secreted by the immune cells, have a definitive role in orchestrating the chemoresistant property of the tumor...
December 23, 2016: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28032590/predicting-the-impact-of-combined-therapies-on-myeloma-cell-growth-using-a-hybrid-multi-scale-agent-based-model
#18
Zhiwei Ji, Jing Su, Dan Wu, Huiming Peng, Weiling Zhao, Brian Nlong Zhao, Xiaobo Zhou
Multiple myeloma is a malignant still incurable plasma cell disorder. This is due to refractory disease relapse, immune impairment, and development of multi-drug resistance. The growth of malignant plasma cells is dependent on the bone marrow (BM) microenvironment and evasion of the host's anti-tumor immune response. Hence, we hypothesized that targeting tumor-stromal cell interaction and endogenous immune system in BM will potentially improve the response of multiple myeloma (MM). Therefore, we proposed a computational simulation of the myeloma development in the complicated microenvironment which includes immune cell components and bone marrow stromal cells and predicted the effects of combined treatment with multi-drugs on myeloma cell growth...
December 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/28030810/the-tumor-microenvironment-promotes-cancer-progression-and-cell-migration
#19
Viviana Salvatore, Gabriella Teti, Stefano Focaroli, Maria Carla Mazzotti, Antonio Mazzotti, Mirella Falconi
The tumor microenvironment contributes to cancer progression, in part through interactions between tumor and normal stromal cells. This study analyzed morphological and molecular changes induced in co-cultured human fibroblasts (HFs) and the MG-63 osteosarcoma cell line. Co-cultured cell monolayers were morphologically analyzed using high resolution scanning electron microscopy (HR-SEM), and trans-well assays were performed to assess cell migration and invasion. Proteins involved in inflammatory responses, cancer cell invasion, and angiogenesis were assessed using western blotting...
December 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/28029610/impact-of-local-injection-of-brain-derived-neurotrophic-factor-expressing-mesenchymal-stromal-cells-mscs-combined-with-intravenous-msc-delivery-in-a-canine-model-of-chronic-spinal-cord-injury
#20
Seung Hoon Lee, Yongsun Kim, Daeun Rhew, Ahyoung Kim, Kwang Rae Jo, Yongseok Yoon, Kyeung Uk Choi, Taeseong Jung, Wan Hee Kim, Oh-Kyeong Kweon
BACKGROUND AIMS: The microenvironment of the chronically injured spinal cord does not allow for axonal regeneration due to glial scarring. To ameliorate this, several therapeutic strategies have been used. We investigated whether combined transplantation of chondroitinase ABC (chABC) and mesenchymal stromal cells (MSCs) genetically modified to secrete brain-derived neurotrophic factor (BDNF) with intravenous (IV) administration of MSCs can promote recovery of hindlimb function after chronic spinal cord injury (SCI)...
October 28, 2016: Cytotherapy
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