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tumor stromal microenvironment

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https://www.readbyqxmd.com/read/28817816/exosomes-derived-from-human-bone-marrow-mesenchymal-stem-cells-promote-tumor-growth-through-hedgehog-signaling-pathway
#1
Jin Qi, Yali Zhou, Zuoyi Jiao, Xu Wang, Yang Zhao, Yangbin Li, Huijuan Chen, Luxi Yang, Hongwen Zhu, Yumin Li
BACKGROUND/AIMS: Mesenchymal stem/stromal cells (MSCs) are known to home to sites of tumor microenvironments where they participate in the formation of the tumor microenvironment and to interplay with tumor cells. However, the potential functional effects of MSCs on tumor cell growth are controversial. Here, we, from the view of bone marrow MSC-derived exosomes, study the molecular mechanism of MSCs on the growth of human osteosarcoma and human gastric cancer cells. METHODS: MSCs derived from human bone marrow (hBMSCs) were isolated and cultured in complete DMEM/F12 supplemented with 10% exosome-depleted fetal bovine serum and 1% penicillin-streptomycin, cell culture supernatants containing exosomes were harvested and exosome purification was performed by ultracentrifugation...
August 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28815347/the-tumor-stromal-ratio-as-a-strong-prognosticator-for-advanced-gastric-cancer-patients-proposal-of-a-new-tsnm-staging-system
#2
Chunwei Peng, Jiuyang Liu, Guifang Yang, Yan Li
BACKGROUND: Insufficient attention is paid to the underlying tumor microenvironment (TME) evolution, that resulting in tumor heterogeneity and driving differences in cancer aggressiveness and treatment outcomes. The morphological evaluation of the proportion of the stroma at the most invasive part of primary tumor (tumor-stromal ratio, TSR) in cancer is gaining momentum as evidence strengthens for the clinical relevance. METHODS: Tissue samples from the most invasive part of the primary gastric cancer (GC) of 494 patients were analyzed for their TSR, and a new TSNM (tumor-stromal node metastasis) staging system based on patho-biological behaviors was established and assessed...
August 16, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28811976/long-lived-pancreatic-ductal-adenocarcinoma-slice-cultures-enable-precise-study-of-the-immune-microenvironment
#3
Xiuyun Jiang, Y David Seo, Jae Hyuck Chang, Andrew Coveler, Eslam N Nigjeh, Sheng Pan, Florencia Jalikis, Raymond S Yeung, Ian N Crispe, Venu G Pillarisetty
Pancreatic ductal adenocarcinoma (PDA) remains a deadly disease that is rarely cured, despite many recent successes with immunotherapy for other malignancies. As the human disease is heavily infiltrated by effector T cells, we postulated that accurately modeling the PDA immune microenvironment would allow us to study mechanisms of immunosuppression that could be overcome for therapeutic benefit. Using viable precision-cut slices from fresh PDA, we developed an organotypic culture system for this purpose. We confirmed that cultured slices maintain their baseline morphology, surface area, and microenvironment after at least 6 d in culture, and demonstrated slice survival by MTT assay and by immunohistochemistry staining with Ki-67 and cleaved-Caspase-3 antibodies...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28798857/the-role-of-shear-stress-and-altered-tissue-properties-on-endothelial-to-mesenchymal-transformation-and-tumor-endothelial-cell-interaction
#4
Sara G Mina, Peter Huang, Bruce T Murray, Gretchen J Mahler
Tumor development is influenced by stromal cells in aspects including invasion, growth, angiogenesis, and metastasis. Activated fibroblasts are one group of stromal cells involved in cancer metastasis, and one source of activated fibroblasts is endothelial to mesenchymal transformation (EndMT). EndMT begins when the endothelial cells delaminate from the cell monolayer, lose cell-cell contacts, lose endothelial markers such as vascular endothelial-cadherin (VE-cadherin), gain mesenchymal markers like alpha-smooth muscle actin (α-SMA), and acquire mesenchymal cell-like properties...
July 2017: Biomicrofluidics
https://www.readbyqxmd.com/read/28790197/breast-tumors-educate-the-proteome-of-stromal-tissue-in-an-individualized-but-coordinated-manner
#5
Xuya Wang, Arshag D Mooradian, Petra Erdmann-Gilmore, Qiang Zhang, Rosa Viner, Sherri R Davies, Kuan-Lin Huang, Ryan Bomgarden, Brian A Van Tine, Jieya Shao, Li Ding, Shunqiang Li, Matthew J Ellis, John C Rogers, R Reid Townsend, David Fenyö, Jason M Held
Cancer forms specialized microenvironmental niches that promote local invasion and colonization. Engrafted patient-derived xenografts (PDXs) locally invade and colonize naïve stroma in mice while enabling unambiguous molecular discrimination of human proteins in the tumor from mouse proteins in the microenvironment. To characterize how patient breast tumors form a niche and educate naïve stroma, subcutaneous breast cancer PDXs were globally profiled by species-specific quantitative proteomics. Regulation of PDX stromal proteins by breast tumors was extensive, with 35% of the stromal proteome altered by tumors consistently across different animals and passages...
August 8, 2017: Science Signaling
https://www.readbyqxmd.com/read/28775118/chronic-lymphocytic-leukemia-cells-are-active-participants-in-microenvironmental-cross-talk
#6
Martijn Ha van Attekum, Eric Eldering, Arnon P Kater
The importance of the tumor microenvironment in chronic lymphocytic leukemia is widely accepted. Yet, the understanding of the complex interplay between the various types of bystander cells and chronic lymphocytic leukemia cells is incomplete. Whereas numerous studies have indicated that bystander cells provide chronic lymphocytic leukemia-supportive functions, it has also become clear that chronic lymphocytic leukemia cells actively engage in the formation of a supportive tumor microenvironment by engaging in several cross-talk mechanisms...
August 3, 2017: Haematologica
https://www.readbyqxmd.com/read/28774797/mesenchymal-stroma-role-in-osteosarcoma-progression
#7
Margherita Cortini, Sofia Avnet, Nicola Baldini
The initiation and progression of malignant tumors are supported by their microenvironment: cancer cells per se cannot explain growth and formation of the primary or metastasis, and a combination of proliferating tumor cells, cancer stem cells, immune cells mesenchymal stromal cells and/or cancer-associated fibroblasts all contribute to the tumor bulk. The interaction between these multiple players, under different microenvironmental conditions of biochemical and physical stimuli (i.e. oxygen tension, pH, matrix mechanics), regulates the production and biological activity of several soluble factors, extracellular matrix components, and extracellular vesicles that are needed for growth, maintenance, chemoresistance and metastatization of cancer...
July 31, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28763139/tumor-endothelial-cells-accelerate-tumor-metastasis
#8
REVIEW
Nako Maishi, Kyoko Hida
Tumor metastasis is the main cause of cancer-related deaths. Understanding the molecular mechanisms underlying tumor metastasis is crucial to control the fatal disease. Several molecular pathways orchestrate the complex cell biological events during a metastatic cascade. It is now well known that bidirectional interaction between the tumor cells and their microenvironment, including tumor stroma, is important for tumor progression and metastasis. Tumor stromal cells, which acquire their specific characteristics in the tumor microenvironment, accelerate tumor malignancy...
August 1, 2017: Cancer Science
https://www.readbyqxmd.com/read/28760449/tumor-microenvironment-determines-response-to-a-heat-activated-thermosensitive-liposome-formulation-of-cisplatin-in-cervical-carcinoma
#9
Yannan N Dou, Naz Chaudary, Martin C Chang, Michael Dunne, Huang Huang, David A Jaffray, Michael Milosevic, Christine Allen
Significant heterogeneity in the tumor microenvironment of human cervical cancer patients is known to challenge treatment outcomes in this population. The current standard of care for cervical cancer patients is radiation therapy and concurrent cisplatin (CDDP) chemotherapy. Yet this treatment strategy fails to control loco-regional disease in 10-30% of patients. In order to improve the loco-regional control rate, a thermosensitive liposome formulation of CDDP (HTLC) was developed to increase local concentrations of drug in response to mild hyperthermia (HT)...
July 29, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28759045/tumor-microenvironment-confers-mtor-inhibitor-resistance-in-invasive-intestinal-adenocarcinoma
#10
T Fujishita, Y Kojima, R Kajino-Sakamoto, M M Taketo, M Aoki
Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is frequently activated in cancers and can be counteracted with the clinical mTORC1 inhibitors everolimus and temsirolimus. Although mTORC1 and dual mTORC1/2 inhibitors are currently under development to treat various malignancies, the emergence of drug resistance has proven to be a major complication. Using the cis-Apc/Smad4 mouse model of locally invasive intestinal adenocarcinoma, we show that administration of everolimus or the dual mTORC1/2 inhibitor AZD8055 significantly reduces the growth of intestinal tumors...
July 31, 2017: Oncogene
https://www.readbyqxmd.com/read/28758931/tumor-stroma-crosstalk-in-bone-tissue-the-osteoclastogenic-potential-of-a-breast-cancer-cell-line-in-a-co-culture-system-and-the-role-of-egfr-inhibition
#11
Laura Mercatali, Federico La Manna, Giacomo Miserocchi, Chiara Liverani, Alessandro De Vita, Chiara Spadazzi, Alberto Bongiovanni, Federica Recine, Dino Amadori, Martina Ghetti, Toni Ibrahim
Although bone metastases represent a major challenge in the natural history of breast cancer (BC), the complex interactions involved have hindered the development of robust in vitro models. The aim of this work is the development of a preclinical model of cancer and bone stromal cells to mimic the bone microenvironment. We studied the effects on osteoclastogenesis of BC cells and Mesenchymal stem cells (MSC) cultured alone or in combination. We also analyzed: (a) whether the blockade of the Epithelial Growth Factor Receptor (EGFR) pathway modified their influence on monocytes towards differentiation, and (b) the efficacy of bone-targeted therapy on osteoclasts...
July 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28757170/the-deleterious-interplay-between-tumor-epithelia-and-stroma-in-cholangiocarcinoma
#12
REVIEW
Massimiliano Cadamuro, Tommaso Stecca, Simone Brivio, Valeria Mariotti, Romina Fiorotto, Carlo Spirli, Mario Strazzabosco, Luca Fabris
Prognosis of cholangiocarcinoma, a devastating liver epithelial malignancy characterized by early invasiveness, remains very dismal, though its incidence has been steadily increasing. Evidence is mounting that in cholangiocarcinoma, tumor epithelial cells establish an intricate web of mutual interactions with multiple stromal components, largely determining the pervasive behavior of the tumor. The main cellular components of the tumor microenvironment (i.e. myofibroblasts, macrophages, lymphatic endothelial cells), which has been recently termed as 'tumor reactive stroma', are recruited and activated by neoplastic cells, and in turn, deleteriously mold tumor behavior by releasing a huge variety of paracrine signals, including cyto/chemokines, growth factors, morphogens and proteinases...
July 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28754894/a-cancer-stem-cell-model-as-the-point-of-origin-of-cancer-associated-fibroblasts-in-tumor-microenvironment
#13
Neha Nair, Anna Sanchez Calle, Maram Hussein Zahra, Marta Prieto-Vila, Aung Ko Ko Oo, Laura Hurley, Arun Vaidyanath, Akimasa Seno, Junko Masuda, Yoshiaki Iwasaki, Hiromi Tanaka, Tomonari Kasai, Masaharu Seno
Cancer-associated fibroblasts (CAFs) are one of the most prominent cell types in the stromal compartment of the tumor microenvironment. CAFs support multiple aspects of cancer progression, including tumor initiation, invasion, and metastasis. The heterogeneous nature of the stromal microenvironment is attributed to the multiple sources from which the cells in this compartment originate. The present study provides the first evidence that cancer stem cells (CSCs) are one of the key sources of CAFs in the tumor niche...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28754819/tumor-purity-as-an-underlying-key-factor-in-glioma
#14
Chuan-Bao Zhang, Wen Cheng, Xiufang Ren, Zheng Wang, Xing Liu, Guanzhang Li, Sheng Han, Tao Jiang, Anhua Wu
 <span style="font-size: 11px;">Glioma tissues consist not only of glioma cells but also glioma-associated non-tumor cells, such as stromal cells and immune cells. These non-tumor cells dilute the purity of glioma cells and play important roles in glioma biology. Currently, the implications of variation in glioma purity are not sufficiently clarified.</span><br /><br /><br />Experimental Design: <span style="font-size: 11px;">Here, tumor purity was inferred for 2249 gliomas and 29 normal brain tissues from five cohorts...
July 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28754674/adipose-progenitor-cell-secretion-of-gm-csf-and-mmp9-promotes-a-stromal-and-immunological-microenvironment-that-supports-breast-cancer-progression
#15
Francesca Reggiani, Valentina Labanca, Patrizia Mancuso, Cristina Rabascio, Giovanna Talarico, Stefania Orecchioni, Andrea Manconi, Francesco Bertolini
A cell population with progenitor-like phenotype (CD45-CD34+) resident in human white adipose tissue (WAT) is known to promote the progression of local and metastatic breast cancer and angiogenesis. However, the molecular mechanisms of the interaction have not been elucidated. In this study, we identified two proteins that were significantly up-regulated in WAT-derived progenitors after co-culture with breast cancer: granulocyte-macrophage colony-stimulating factor (GM-CSF) and matrix metallopeptidase 9 (MMP9)...
July 28, 2017: Cancer Research
https://www.readbyqxmd.com/read/28754000/the-role-of-tumor-microenvironment-in-chemoresistance-to-survive-keep-your-enemies-closer
#16
REVIEW
Dimakatso Alice Senthebane, Arielle Rowe, Nicholas Ekow Thomford, Hendrina Shipanga, Daniella Munro, Mohammad A M Al Mazeedi, Hashim A M Almazyadi, Karlien Kallmeyer, Collet Dandara, Michael S Pepper, M Iqbal Parker, Kevin Dzobo
Chemoresistance is a leading cause of morbidity and mortality in cancer and it continues to be a challenge in cancer treatment. Chemoresistance is influenced by genetic and epigenetic alterations which affect drug uptake, metabolism and export of drugs at the cellular levels. While most research has focused on tumor cell autonomous mechanisms of chemoresistance, the tumor microenvironment has emerged as a key player in the development of chemoresistance and in malignant progression, thereby influencing the development of novel therapies in clinical oncology...
July 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28753587/combined-prognostic-effect-of-pd-l1-expression-and-immunoscore-in-microsatellite-unstable-advanced-gastric-cancers
#17
Kyung-Ju Kim, Han Kwang Yang, Woo Ho Kim, Gyeong Hoon Kang
BACKGROUND: The aim of this study was to evaluate how programmed death-ligand-1 (PD-L1) expression is linked to the immunoscore in the context of the tumor microenvironment and to assess the differential prognostic value of PD-L1 expression according to the immunoscore in 153 patients with microsatellite instability-high (MSI-H) advanced gastric cancer (GC). RESULTS: We found that T-PD-L1 (+) and I-PD-L1 (+) were significantly associated with a high immunoscore...
July 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28746017/tumor-evolution-heterogeneity-and-therapy-for-our-patients-with-advanced-cancer-how-far-have-we-come
#18
Wafik S El-Deiry, Barry Taylor, Joel W Neal
The clinical and molecular heterogeneity of various cancer types is well documented. In the era of precision oncology whereby molecular profiling of tumors is incorporated into clinical care, both intra- and intertumoral molecular and genetic heterogeneity have been described. Together, they impact patient treatment and outcomes. Host genetics and the tumor microenvironment impact on tumor evolution and heterogeneity through variations in immune cell infiltration, stromal variations, and selection pressures from hypoxia or nutrient stress, among others...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28741502/immune-priming-of-the-tumor-microenvironment-by-radiation
#19
REVIEW
Wen Jiang, Charles K Chan, Irving L Weissman, Betty Y S Kim, Stephen M Hahn
Ionizing irradiation can induce a multitude of alterations within the tumor microenvironment. Unlike targeted therapies, radiation delivered to the tumor bed can prompt phenotypic changes in both normal stromal and cancer cells, leading to molecular and physiological alterations within the tumor microenvironment. These environmental modulations directly influence the degree of immunogenicity of the tumor microenvironment and may ultimately affect tumor responsiveness to cancer immunotherapies. Here we review the preclinical evidence for tumor microenvironment-mediated immune suppression and how radiation can modulate immune properties within a tumor...
November 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28731046/pd-l1-expression-and-the-immune-microenvironment-in-primary-invasive-lobular-carcinomas-of-the-breast
#20
Elizabeth D Thompson, Janis M Taube, Rebecca J Asch-Kendrick, Aleksandra Ogurtsova, Haiying Xu, Rajni Sharma, Alan Meeker, Pedram Argani, Leisha A Emens, Ashley Cimino-Mathews
Tumor-infiltrating lymphocytes and immune checkpoint proteins such as PD-L1 are potential prognostic factors and therapeutic targets in breast cancer. Most studies characterizing the breast tumor immune microenvironment have focused on ductal carcinomas. Here we investigate the tumor microenvironment of primary invasive lobular carcinomas. Previously constructed tissue microarrays of 47 lobular carcinomas were labeled by immunohistochemistry for PD-L1, CD8, CD20, and FoxP3. The stromal immune infiltrate density was qualitatively scored as a percentage of tumor area: 1+ (<5%); 2+ (5-10%); 3+ (10-15%); or 4+ (>50%)...
July 21, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
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