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tumor stromal microenvironment

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https://www.readbyqxmd.com/read/29332341/association-of-the-combined-parameters-including-the-frequency-of-primary-cilia-cd8-tumor-infiltrating-lymphocytes-and-pd-1-expression-with-the-outcome-in-intestinal-cancer
#1
Josef Dvorak, Dimitar Hadzi Nikolov, Ladislav Dusek, Alzbeta Filipova, Igor Richter, David Buka, Ales Ryska, Jaroslav Mokry, Stanislav Filip, Bohuslav Melichar, Tomas Buchler, Jitka Abrahamova
PURPOSE: Primary cilium (PC) is considered to be a functional homologue of the immune synapse. Microtubule structures, PC of cancer associated fibroblasts and immune synapses between cytotoxic CD8+ tumor infiltrating lymphocytes (TILs) and cancer cells, are regularly found in varying amounts in the microenvironment of solid tumors. The purpose of this study was to find out the potential association and combined prognostic significance of the frequency of PC, PD-1 and CD8+ TILs in patients with intestinal cancer...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29326121/modeling-multiple-myeloma-bone-marrow-interactions-and-response-to-drugs-in-a-3d-surrogate-microenvironment
#2
Daniela Belloni, Silvia Heltai, Maurilio Ponzoni, Antonello Villa, Barbara Vergani, Lorenza Pecciarini, Magda Marcatti, Stefania Girlanda, Giovanni Tonon, Fabio Ciceri, Federico Caligaris-Cappio, Marina Ferrarini, Elisabetta Ferrero
Multiple myeloma develops primarily inside the bone marrow microenvironment, that confers pro-survival signals and drug resistance. 3D cultures that reproduce multiple myeloma-bone marrow interactions are needed to fully investigate multiple myeloma pathogenesis and response to drugs. To this purpose, we exploited the 3D Rotary Cell Culture System bioreactor technology for myeloma-bone marrow co-cultures in gelatin scaffolds. The model was validated with myeloma cell lines that, as assessed by histochemical and electron-microscopic analyses, engaged contacts with stromal cells and endothelial cells...
January 11, 2018: Haematologica
https://www.readbyqxmd.com/read/29322415/laser-microdissection-of-cellular-compartments-for-expression-analyses-in-cancer-models
#3
Tae-Su Han, Masanobu Oshima
Cancer tissues are composed of various cell types including cancer cells, cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs) and endothelial cells. These surrounding stromal cells form the tumor microenvironment, partly through the inflammatory response, which plays an important role in the development and malignant progression of cancer. It is therefore important to examine the expression profiles and protein modifications of each cellular component independently to decipher the interaction between the tumor cells and the microenvironment...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29318554/evaluation-of-tumor-vasculature-using-a-syngeneic-tumor-model-in-wild-type-and-genetically-modified-mice
#4
Francisco Javier Rodríguez-Baena, Silvia Redondo-García, María Del Carmen Plaza-Calonge, Rubén Fernández-Rodríguez, Juan Carlos Rodríguez-Manzaneque
The relevance of tumor vasculature has been extensively recognized, and it is still the focus of numerous lines of research for basic, translational, and clinical scientists. Indeed, the knowledge of some of its regulatory mechanisms has provoked the generation of ongoing cancer therapies. Within the context of the tumor microenvironment, the information that the analysis of the vasculature provides is very valuable, and it might reveal not just its quality and the response against a specific therapy but also its close relationship with neighboring stromal and tumor players...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29315233/dissecting-time-from-tumor-related-gene-expression-variability-in-bilateral-breast-cancer
#5
Maurizio Callari, Matteo Dugo, Patrizia Miodini, Silvia Veneroni, Giampaolo Bianchini, Maria Grazia Daidone, Vera Cappelletti
Metachronous (MBC) and synchronous bilateral breast tumors (SBC) are mostly distinct primaries, whereas paired primaries and their local recurrences (LRC) share a common origin. Intra-pair gene expression variability in MBC, SBC, and LRC derives from time/tumor microenvironment-related and tumor genetic background-related factors and pairs represents an ideal model for trying to dissect tumor-related from microenvironment-related variability. Pairs of tumors derived from women with SBC (n = 18), MBC (n = 11), and LRC (n = 10) undergoing local-regional treatment were profiled for gene expression; similarity between pairs was measured using an intraclass correlation coefficient (ICC) computed for each gene and compared using analysis of variance (ANOVA)...
January 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29301792/therapy-educated-mesenchymal-stem-cells-enrich-for-tumor-initiating-cells
#6
Michael Timaner, Nitzan Letko-Khait, Ruslana Kotsofruk, Madeleine Benguigui, Ofrat Beyar-Katz, Chen Rachman-Tzemach, Ziv Raviv, Tomer Bronshtein, Marcelle Machluf, Yuval Shaked
Stromal cells residing in the tumor microenvironment contribute to the development of therapy resistance. Here we show that chemotherapy-educated mesenchymal stem cells (MSCs) promote therapy resistance via crosstalk with tumor-initiating cells (TICs), a resistant tumor cell subset that initiates tumorigenesis and metastasis. In response to gemcitabine chemotherapy, MSCs colonized pancreatic adenocarcinomas in large numbers and resided in close proximity to TICs. Furthermore, gemcitabine-educated MSCs promoted the enrichment of TICs in vitro and enhance tumor growth in vivo...
January 4, 2018: Cancer Research
https://www.readbyqxmd.com/read/29301607/force-mediated-proinvasive-matrix-remodeling-driven-by-tumor-associated-mesenchymal-stem-like-cells-in-glioblastoma
#7
Eun-Jung Lim, Yongjoon Suh, Seungmo Kim, Seok-Gu Kang, Su-Jae Lee
In carcinoma, cancer-associated fibroblasts participate in force-mediated extracellular matrix (ECM) remodeling, consequently leading to invasion of cancer cells. Likewise, the ECM remodeling actively occurs in glioblastoma (GBM) and the consequent microenvironmental stiffness is strongly linked to migration behavior of GBM cells. However, in GBM the stromal cells responsible for force-mediated ECM remodeling remain unidentified. We show that tumor-associated mesenchymal stem-like cells (tMSLCs) provide a proinvasive matrix condition in GBM by force-mediated ECM remodeling...
January 5, 2018: BMB Reports
https://www.readbyqxmd.com/read/29301448/targeting-tumor-microenvironment-to-curb-chemoresistance-via-novel-drug-delivery-strategies
#8
Chintan Bhavsar, Munira Momin, Tabassum Khan, Abdelwahab Omri
A tumor is a heterogeneous mass of malignant cells that co-exists with non-malignant cells. The co-existence evolves from the initial developmental stages of the tumor and is one of the hallmarks of cancer. The presence of non-malignant cells provides a pro-tumorigenic niche known as the tumor microenvironment (TME). Proliferation, invasiveness, metastatic potential and maintenance of stemness through cross-talk between tumors and tumor associated stromal cells (TASCs) forms the basis of TME. Areas covered: The article highlights the developmental phases of a tumor from dysplasia to an invasive condition leading to formation of clinically detectable tumors...
January 4, 2018: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/29298894/tumor-extrinsic-discoidin-domain-receptor-1-promotes-mammary-tumor-growth-by-regulatingadipose-stromal-interleukin-6-production-in-mice
#9
Xiujie Sun, Kshama Gupta, Bogang Wu, Deyi Zhang, Bin Yuan, Xiaowen Zhang, Huai-Chin Chiang, Chi Zhang, Tyler J Curiel, Michelle P Bendeck, Stephen Hursting, Yanfen Hu, Rong Li
Discoidin domain receptor 1 (DDR1) is a collagen receptor that mediates cell communications with the extracellular matrix (ECM). Aberrant expression and activity of DDR1 in tumor cells are known to promote tumor growth. Although elevated DDR1 levels in stroma of breast tumors are associated with poor patient outcome, a causal role for tumor-extrinsic DDR1 in cancer promotion remains unclear, however. Here, we report that murine mammary tumor cells transplanted to syngeneic recipient mice in which Ddr1 has been knocked out (KO) grow less robustly than in WT mice...
January 3, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29297942/expression-pattern-of-immunosurveillance-related-antigen-in-adult-t-cell-leukemia-lymphoma
#10
Naoko Asano, Hiroaki Miyoshi, Takeharu Kato, Joji Shimono, Noriaki Yoshida, Daisuke Kurita, Yuya Sasaki, Keisuke Kawamoto, Koichi Ohshima, Masao Seto
AIMS: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with a poor prognosis. Human leukocyte antigen (HLA) and β2M serve as key molecules in tumor immunity, and their expression is frequently reduced in tumor cells. Programmed cell death (PD)-1/PD-ligand1 (PD-L1) interactions play a role in escape of tumor cells from T-cell immunity. Therefore, this study aimed to determine the clinicopathological relevance of HLA and β2M expressions in ATLL cells and PD-L1 expression in lymphoma or stromal cells and predict the overall survival of patients with ATLL...
January 3, 2018: Histopathology
https://www.readbyqxmd.com/read/29296768/patient-derived-xenografts-of-low-grade-b-cell-lymphomas-demonstrate-roles-of-the-tumor-microenvironment
#11
W Richard Burack, Janice M Spence, John P Spence, Stephen A Spence, Philip J Rock, Gautam N Shenoy, Leonard D Shultz, Richard B Bankert, Steven H Bernstein
To discern features of non-Hodgkin lymphomas (NHL) that are autonomous from those that are shaped by the tumor environment (TE), we used patient-derived xenografts (PDX) to probe the effects on neoplastic cells of manipulating the TE. Properties of neoplastic cells that are often considered to be autonomous include their relative independence from stromal support, their relative survival and/or proliferation advantages compared with nonneoplastic cells, and their state of differentiation. Prior approaches to creation of PDX models likely select for neoplasms, which are the most capable of engraftment, potentially masking the effects of the TE...
July 11, 2017: Blood Advances
https://www.readbyqxmd.com/read/29290958/stromal-annexin-a2-expression-is-predictive-of-decreased-survival-in-pancreatic-cancer
#12
Adrian G Murphy, Kelly Foley, Agnieszka A Rucki, Tao Xia, Elizabeth M Jaffee, Chiung-Yu Huang, Lei Zheng
Pancreatic ductal adenocarcinoma (PDA) is renowned for high rates of metastasis and poor survival. Its notoriously dense fibrotic stroma contributes to chemoresistance. Stromal signaling in PDA is recognized for its multiple roles in regulating tumor invasion and metastasis. However, no stromal biomarker which can predict survival in PDA exists. Annexin A2 (AnxA2) was formerly identified as a metastasis-associated protein in PDA and tumoral overexpression is associated with poor survival. In this study, we examined AnxA2 expression in the tumor microenvironment in a preclinical model of PDA which suggests its role in tumor colonization...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290263/abundant-tumor-promoting-stromal-cells-in-lung-adenocarcinoma-with-hypoxic-regions
#13
Hiroshi Nakamura, Tomohiro Ichikawa, Shoko Nakasone, Tomohiro Miyoshi, Masato Sugano, Motohiro Kojima, Satoshi Fujii, Atsushi Ochiai, Takeshi Kuwata, Keiju Aokage, Kenji Suzuki, Masahiro Tsuboi, Genichiro Ishii
OBJECTIVES: Carbonic anhydrase IX (CAIX) is a marker of hypoxia and its expression by cancer associated fibroblasts (CAFs) was reportedly associated with the poor prognosis of lung adenocarcinoma. This study aimed to characterize the hypoxic microenvironment containing CAIX (+) CAFs. MATERIALS AND METHODS: First, we evaluated the clinicopathological significance of CAIX expression by CAFs in 3cm and above lung adenocarcinoma (n=188). We then compared the expressions of E-cadherin, ezrin, ALDH-1, CD44, EGFR, HSF-1, Glut-1, and PD-L1 in cancer cells, as well as those of CD204 and podoplanin in stromal cells between CAIX (+) CAFs and CAIX (-) CAFs cases (n=25, each)...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29289420/exosome-and-mesenchymal-stem-cell-cross-talk-in-the-tumor-microenvironment
#14
REVIEW
Theresa L Whiteside
Mesenchymal stem cells (MSCs) are a major component of the tumor microenvironment (TME) and play a key role in promoting tumor progression. The tumor uses exosomes to co-opt MSCs and re-program their functional profile from normally trophic to pro-tumorigenic. These tumor-derived small vesicles called "TEX" carry and deliver a cargo rich in proteins and nucleic acids to MSCs. Upon interactions with surface receptors on MSCs and uptake of the exosome cargo by MSCs, molecular, transcriptional and translational changes occur that convert MSCs into producers of factors that are necessary for tumor growth and that also alter functions of non-tumor cells in the TME...
December 27, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/29285283/diffusion-weighted-mri-derived-adc-values-reflect-collagen-i-content-in-pdx-models-of-uterine-cervical-cancer
#15
Anette Hauge, Catherine S Wegner, Jon-Vidar Gaustad, Trude G Simonsen, Lise Mari K Andersen, Einar K Rofstad
Apparent diffusion coefficient (ADC) values derived from diffusion-weighted magnetic resonance imaging (DW-MRI) are known to reflect the cellular environment of biological tissues. However, emerging evidence accentuates the influence of stromal elements on ADC values. The current study sought to elucidate whether a correlation exists between ADC and the fraction of collagen I-positive tissue across different tumor models of uterine cervical cancer. Early and late generation tumors of four patient-derived xenograft (PDX) models of squamous cell carcinoma (BK-12, ED-15, HL-16, and LA-19) were included...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29275475/imaging-the-tumor-microenvironment
#16
Marie-Caline Z Abadjian, W Barry Edwards, Carolyn J Anderson
The tumor microenvironment consists of tumor, stromal, and immune cells, as well as extracellular milieu. Changes in numbers of these cell types and their environments have an impact on cancer growth and metastasis. Non-invasive imaging of aspects of the tumor microenvironment can provide important information on the aggressiveness of the cancer, whether or not it is metastatic, and can also help to determine early response to treatment. This chapter provides an overview on non-invasive in vivo imaging in humans and mouse models of various cell types and physiological parameters that are unique to the tumor microenvironment...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29275043/signatures-of-protein-expression-revealed-by-secretome-analyses-of-cancer-associated-fibroblasts-and-melanoma-cell-lines
#17
Tarcísio Liberato, Dayelle S Pessotti, Isabella Fukushima, Eduardo S Kitano, Solange M T Serrano, André Zelanis
The imbalance of cellular homeostasis during oncogenesis together with the high heterogeneity of tumor-associated stromal cells have a marked effect on the repertoire of the proteins secreted by malignant cells (the secretome). Hence, the study of tumoral secretomes provides insights for understanding the cross-talk between cells within the tumor microenvironment as well as the key effectors for the establishment of the pre-metastatic niche in distant tumor sites. In this context, we performed a proteomic analysis of the secretomes derived from four cell lines: a paired set of fibroblasts - Hs 895...
December 21, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/29273955/prognostic-value-of-tumor-stroma-ratio-combined-with-the-immune-status-of-tumors-in-invasive-breast-carcinoma
#18
K M H Vangangelt, G W van Pelt, C C Engels, H Putter, G J Liefers, V T H B M Smit, R A E M Tollenaar, P J K Kuppen, W E Mesker
PURPOSE: Complex interactions occur between cancer cells and cells in the tumor microenvironment. In this study, the prognostic value of the interplay between tumor-stroma ratio (TSR) and the immune status of tumors in breast cancer patients was evaluated. METHODS: A cohort of 574 breast cancer patients was analyzed. The percentage of tumor stroma was visually estimated on Hematoxylin and Eosin (H&E) stained histological tumor tissue sections. Immunohistochemical staining was performed for classical human leukocyte antigen (HLA) class I, HLA-E, HLA-G, markers for regulatory T (Treg) cells, natural killer (NK) cells and cytotoxic T-lymphocytes (CTLs)...
December 22, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29273462/fibroblast-activation-proteins-%C3%AE-suppress-tumor-immunity-by-regulating-t-cells-and-tumor-associated-macrophages
#19
Chun Mei Hou, Xue Mei Qu, Jian Zhang, Ting Ting Ding, Wei Han, Guang Chuan Ji, Zhao Hua Zhong, He Chen, Feng-Min Zhang
Fibroblast activation protein-α (FAPα) is a type-II cell-surface-bound integral transmembrane serine protease and selectively overexpressed by tumor-associated stromal fibroblasts (TAFs), which are the main components in the tumor microenvironment, in >90% of malignant epithelial carcinomas. FAPα regulates the immunosuppression of tumor cells in the tumor microenvironment. Regulatory T cells (Tregs) and tumor-associated macrophages (TAMs) are the major immunosuppressive cells in the tumor microenvironment...
December 19, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29259267/dysregulation-of-mir-196b-in-head-and-neck-cancers-leads-to-pleiotropic-effects-in-the-tumor-cells-and-surrounding-stromal-fibroblasts
#20
Saúl Álvarez-Teijeiro, Sofía T Menéndez, M Ángeles Villaronga, Juan P Rodrigo, Lorea Manterola, Lucas de Villalaín, Juan C de Vicente, Laura Alonso-Durán, M Pilar Fernández, Charles H Lawrie, Juana M García-Pedrero
The miR-196 family members have been found dysregulated in different cancers. Therefore, they have been proposed as promising biomarkers and therapeutic targets. This study is the first to investigate the role of miR-196b in the development and progression of head and neck squamous cell carcinomas (HNSCC), and also the impact on the surrounding tumor microenvironment. Increased miR-196b levels were detected in 95% of primary tumors and precancerous lesions, although no significant differences were observed between non-progressing versus progressing dysplasias...
December 19, 2017: Scientific Reports
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