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https://www.readbyqxmd.com/read/29163806/interferon-inducible-cxc-chemokines-are-crucial-immune-modulators-and-survival-predictors-in-colorectal-cancer
#1
Larissa Kistner, Dietrich Doll, Anne Holtorf, Ulrich Nitsche, Klaus-Peter Janssen
Tumor-infiltrating T-cells are strongly associated with prognosis in colorectal cancer, but the mechanisms governing intratumoral lymphocyte recruitment are unclear. We investigated the clinical relevance and functional contribution of interferon-regulated CXC-chemokines CXCL9, CXCL10, and CXCL11, described as T-cells attractants. Their expression was significantly elevated in tumors as compared to normal colon in 163 patients with colon cancer, represented an independent positive predictor of post-operative survival, and was highly significantly correlated with the presence of tumor-infiltrating cytotoxic CD8(+) T-cells and CD4(+) TH1-effector cells...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29044515/the-human-pkp2-plakophilin-2-gene-is-induced-by-wnt-%C3%AE-catenin-in-normal-and-colon-cancer-associated-fibroblasts
#2
Núria Niell, María Jesús Larriba, Gemma Ferrer-Mayorga, Isabel Sánchez-Pérez, Ramón Cantero, Francisco X Real, Luis Del Peso, Alberto Muñoz, José Manuel González-Sancho
Colorectal cancer results from the malignant transformation of colonic epithelial cells. Stromal fibroblasts are the main component of the tumour microenvironment, and play an important role in the progression of this and other neoplasias. Wnt/β-catenin signalling is essential for colon homeostasis, but aberrant, constitutive activation of this pathway is a hallmark of colorectal cancer. Here we present the first transcriptomic study on the effect of a Wnt factor on human colonic myofibroblasts. Wnt3A regulates the expression of 1,136 genes, of which 662 are upregulated and 474 are downregulated in CCD-18Co cells...
October 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29032203/construction-of-artificial-human-peritoneal-tissue-by-cell-accumulation-technique-and-its-application-for-visualizing-morphological-dynamics-of-cancer-peritoneal-metastasis
#3
Yoshiya Asano, Tadashi Odagiri, Hiroe Oikiri, Michiya Matsusaki, Mitsuru Akashi, Hiroshi Shimoda
Human peritoneum is composed of mesothelial monolayer and stromal tissue containing microvasculature. Dissemination and infiltration of cancer cells to the peritoneum result in cancer peritoneal metastasis which is an important prognostic factor of intraperitoneal or intrapelvic carcinoma. To elucidate an initial metastatic mechanism of cancer cells, in vitro human peritoneal models are demanded. In this study, we created a three-dimensional artificial human peritoneal tissue (AHPT) harboring the blood or lymphatic vascular network by cell-accumulation technique...
October 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29030636/cancer-associated-fibroblasts-induce-metalloprotease-independent-cancer-cell-invasion-of-the-basement-membrane
#4
Alexandros Glentis, Philipp Oertle, Pascale Mariani, Aleksandra Chikina, Fatima El Marjou, Youmna Attieh, Francois Zaccarini, Marick Lae, Damarys Loew, Florent Dingli, Philemon Sirven, Marie Schoumacher, Basile G Gurchenkov, Marija Plodinec, Danijela Matic Vignjevic
At the stage of carcinoma in situ, the basement membrane (BM) segregates tumor cells from the stroma. This barrier must be breached to allow dissemination of the tumor cells to adjacent tissues. Cancer cells can perforate the BM using proteolysis; however, whether stromal cells play a role in this process remains unknown. Here we show that an abundant stromal cell population, cancer-associated fibroblasts (CAFs), promote cancer cell invasion through the BM. CAFs facilitate the breaching of the BM in a matrix metalloproteinase-independent manner...
October 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29017054/the-stromal-niche-for-epithelial-stem-cells-a-template-for-regeneration-and-a-brake-on-malignancy
#5
REVIEW
Kelsey J Roberts, Aaron M Kershner, Philip A Beachy
Stromal restraint of cancer growth and progression-emerging as a widespread phenomenon in epithelial cancers such as bladder, pancreas, colon, and prostate-appears rooted in stromal cell niche activity. During normal tissue repair, stromal niche signals, often Hedgehog-induced, promote epithelial stem cell differentiation as well as self-renewal, thus specifying a regenerating epithelial pattern. In the case of cancerous tissue, stromal cell-derived differentiation signals in particular may provide a brake on malignant growth...
October 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28980848/tumor-stroma-ratio-predicts-recurrence-in-patients-with-colon-cancer-treated-with-neoadjuvant-chemotherapy
#6
Torben Frøstrup Hansen, Sanne Kjær-Frifeldt, Jan Lindebjerg, Søren Rafael Rafaelsen, Lars Henrik Jensen, Anders Jakobsen, Flemming Brandt Sørensen
BACKGROUND: Neoadjuvant chemotherapy represents a new treatment approach to locally advanced colon cancer. The aim of this study was to analyze the ability of tumor-stroma ratio (TSR) to predict disease recurrence in patients with locally advanced colon cancer treated with neoadjuvant chemotherapy. MATERIAL AND METHODS: This study included 65 patients with colon cancer treated with neoadjuvant chemotherapy in a phase II trial. All patients were planned for three cycles of capecitabine and oxaliplatin before surgery...
October 5, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28956065/the-peritoneal-soil-for-a-cancerous-seed-a-comprehensive-review-of-the-pathogenesis-of-intraperitoneal-cancer-metastases
#7
REVIEW
Justyna Mikuła-Pietrasik, Paweł Uruski, Andrzej Tykarski, Krzysztof Książek
Various types of tumors, particularly those originating from the ovary and gastrointestinal tract, display a strong predilection for the peritoneal cavity as the site of metastasis. The intraperitoneal spread of a malignancy is orchestrated by a reciprocal interplay between invading cancer cells and resident normal peritoneal cells. In this review, we address the current state-of-art regarding colonization of the peritoneal cavity by ovarian, colorectal, pancreatic, and gastric tumors. Particular attention is paid to the pro-tumoral role of various kinds of peritoneal cells, including mesothelial cells, fibroblasts, adipocytes, macrophages, the vascular endothelium, and hospicells...
September 27, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28940664/a-novel-histological-examination-with-dynamic-3d-reconstruction-from-multiple-immunohistochemically-stained-sections-of-a-programmed-cell-death-ligand-1-positive-colon-cancer
#8
Shotaro Korehisa, Tetsuo Ikeda, Shinji Okano, Hiroshi Saeki, Eiji Oki, Yoshinao Oda, Makoto Hashizume, Yoshihiko Maehara
AIMS: Programmed cell death-ligand 1 (PD-L1) expression is observed in patients with high level microsatellite instability (MSI-H) colon cancer, which is susceptible to immune checkpoint blockade. The aim of this study was to investigate the interrelationship between PD-L1-positive cells and cytotoxic T cells, lymphatic vessels, and vascular endothelium using histological examination with the three-dimensional (3D) reconstruction of a PD-L1-positive colon cancer. METHODS AND RESULTS: Serial sections of MSI-H colon cancer tissue were stained with haematoxylin and eosin (H&E) and Masson trichrome stains; PD-L1, CD8, D2-40, and CD31 immunohistochemistry were performed...
September 21, 2017: Histopathology
https://www.readbyqxmd.com/read/28931753/ask1-dependent-endothelial-cell-activation-is-critical-in-ovarian-cancer-growth-and-metastasis
#9
Mingzhu Yin, Huanjiao Jenny Zhou, Jiqin Zhang, Caixia Lin, Hongmei Li, Xia Li, Yonghao Li, Haifeng Zhang, David G Breckenridge, Weidong Ji, Wang Min
We have recently reported that tumor-associated macrophages (TAMs) promote early transcoelomic metastasis of ovarian cancer by facilitating TAM-ovarian cancer cell spheroid formation. ASK1 is known to be important for macrophage activation and inflammation-mediated tumorigenesis. In the present study, we show that ASK1 deficiency attenuates TAM-spheroid formation and ovarian cancer progression in an orthotopic ovarian cancer model. Interestingly, ASK1 in stroma, but not in TAMs, is critical for peritoneal tumor growth of ovarian cancer...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28916657/tenascin-c-and-integrin-%C3%AE-9-mediate-interactions-of-prostate-cancer-with-the-bone-microenvironment
#10
Rebeca San Martin, Ravi Pathak, Antrix Jain, Sung Yun Jung, Susan G Hilsenbeck, María C Piña-Barba, Andrew G Sikora, Kenneth J Pienta, David R Rowley
Deposition of the extracellular matrix protein tenascin-C is part of the reactive stroma response, which has a critical role in prostate cancer progression. Here, we report that tenascin C is expressed in the bone endosteum and is associated with formation of prostate bone metastases. Metastatic cells cultured on osteo-mimetic surfaces coated with tenascin C exhibited enhanced adhesion and colony formation as mediated by integrin α9β1. In addition, metastatic cells preferentially migrated and colonized tenascin-C-coated trabecular bone xenografts in a novel system that employed chorioallantoic membranes of fertilized chicken eggs as host...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28911825/paving-the-rho-in-cancer-metastasis-rho-gtpases-and-beyond
#11
REVIEW
Sepp Jansen, Reinoud Gosens, Thomas Wieland, Martina Schmidt
Malignant carcinomas are often characterized by metastasis, the movement of carcinoma cells from a primary site to colonize distant organs. For metastasis to occur, carcinoma cells first must adopt a pro-migratory phenotype and move through the surrounding stroma towards a blood or lymphatic vessel. Currently, there are very limited possibilities to target these processes therapeutically. The family of Rho GTPases is an ubiquitously expressed division of GTP-binding proteins involved in the regulation of cytoskeletal dynamics and intracellular signaling...
September 11, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28889371/bone-marrow-stroma-and-vascular-contributions-to-myeloma-bone-homing
#12
REVIEW
Michele Moschetta, Yawara Kawano, Antonio Sacco, Angelo Belotti, Rossella Ribolla, Marco Chiarini, Viviana Giustini, Diego Bertoli, Alessandra Sottini, Monica Valotti, Claudia Ghidini, Federico Serana, Michele Malagola, Luisa Imberti, Domenico Russo, Alessandro Montanelli, Giuseppe Rossi, Michaela R Reagan, Patricia Maiso, Bruno Paiva, Irene M Ghobrial, Aldo M Roccaro
PURPOSE OF THE REVIEW: Herein we dissect mechanisms behind the dissemination of cancer cells from primary tumor site to the bone marrow, which are necessary for metastasis development, with a specific focus on multiple myeloma. RECENT FINDINGS: The ability of tumor cells to invade vessels and reach the systemic circulation is a fundamental process for metastasis development; however, the interaction between clonal cells and the surrounding microenvironment is equally important for supporting colonization, survival, and growth in the secondary sites of dissemination...
October 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28865407/immunoglobulin-free-light-chains-in-the-pathogenesis-of-lung-disorders
#13
Esmaeil Mortaz, Ian M Adcock, Hamidreza Jamaati, Adnan Khosravi, Masoud Movassaghi, Johan Garssen, Mostafa Alavi Mogadam, Frank A Redegeld
Inflammation is an important component of numerous cancers and chronic diseases and many inflammatory mediators have been shown to have potential prognostic roles. Tumor-infiltrating mast cells can promote tumor growth and angiogenesis, but the mechanism of mast cell activation is unclear. Early studies have shown that immunoglobulin free light chains (FLC) can trigger mast cell activation in an antigen-specific manner. Increased expression of FLC is observed within the stroma of many human cancers including those of breast, colon, lung, pancreas, kidney, and skin...
August 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28846107/nuclear-factor-e2-related-factor-2-has-a-differential-impact-on-mct1-and-mct4-lactate-carrier-expression-in-colonic-epithelial-cells-a-condition-favoring-metabolic-symbiosis-between-colorectal-cancer-and-stromal-cells
#14
K Diehl, L-A Dinges, O Helm, N Ammar, D Plundrich, A Arlt, C Röcken, S Sebens, H Schäfer
Malignant tumors, such as colorectal cancer (CRC), are heterogeneous diseases characterized by distinct metabolic phenotypes. These include Warburg- and reverse Warburg phenotypes depending on differential distribution of the lactate carrier proteins monocarboxylate transporter-4 and -1 (MCT4 and MCT1). Here, we elucidated the role of the antioxidant transcription factor nuclear factor E2-related factor-2 (Nrf2) as the key regulator of cellular adaptation to inflammatory/environmental stress in shaping the metabolism toward a reverse Warburg phenotype in malignant and premalignant colonic epithelial cells...
August 28, 2017: Oncogene
https://www.readbyqxmd.com/read/28814667/adrenergic-mediated-increases-in-inhba-drive-caf-phenotype-and-collagens
#15
Archana S Nagaraja, Robert L Dood, Guillermo Armaiz-Pena, Yu Kang, Sherry Y Wu, Julie K Allen, Nicholas B Jennings, Lingegowda S Mangala, Sunila Pradeep, Yasmin Lyons, Monika Haemmerle, Kshipra M Gharpure, Nouara C Sadaoui, Cristian Rodriguez-Aguayo, Cristina Ivan, Ying Wang, Keith Baggerly, Prahlad Ram, Gabriel Lopez-Berestein, Jinsong Liu, Samuel C Mok, Lorenzo Cohen, Susan K Lutgendorf, Steve W Cole, Anil K Sood
Adrenergic signaling is known to promote tumor growth and metastasis, but the effects on tumor stroma are not well understood. An unbiased bioinformatics approach analyzing tumor samples from patients with known biobehavioral profiles identified a prominent stromal signature associated with cancer-associated fibroblasts (CAFs) in those with a high biobehavioral risk profile (high Center for Epidemiologic Studies Depression Scale [CES-D] score and low social support). In several models of epithelial ovarian cancer, daily restraint stress resulted in significantly increased CAF activation and was abrogated by a nonspecific β-blocker...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28790197/breast-tumors-educate-the-proteome-of-stromal-tissue-in-an-individualized-but-coordinated-manner
#16
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/28769537/osteopontin-at-the-crossroads-of-inflammation-and-tumor-progression
#17
REVIEW
Luigi Mario Castello, Davide Raineri, Livia Salmi, Nausicaa Clemente, Rosanna Vaschetto, Marco Quaglia, Massimiliano Garzaro, Sergio Gentilli, Paolo Navalesi, Vincenzo Cantaluppi, Umberto Dianzani, Anna Aspesi, Annalisa Chiocchetti
Complex interactions between tumor and host cells regulate systemic tumor dissemination, a process that begins early at the primary tumor site and goes on until tumor cells detach themselves from the tumor mass and start migrating into the blood or lymphatic vessels. Metastatic cells colonize the target organs and are capable of surviving and growing at distant sites. In this context, osteopontin (OPN) appears to be a key determinant of the crosstalk between cancer cells and the host microenvironment, which in turn modulates immune evasion...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28764929/inhibition-of-aurora-kinase-a-induces-necroptosis-in%C3%A2-pancreatic%C3%A2-carcinoma
#18
Yangchun Xie, Shan Zhu, Meizuo Zhong, Manhua Yang, Xiaofan Sun, Jinbao Liu, Guido Kroemer, Michael Lotze, Herbert J Zeh, Rui Kang, Daolin Tang
BACKGROUND & AIMS: Induction of nonapoptotic cell death could be an approach to eliminate apoptosis-resistant tumors. We investigated necroptosis-based therapies in mouse models of pancreatic ductal adenocarcinoma cancer (PDAC). METHODS: We screened 273 commercially available kinase inhibitors for cytotoxicity against a human PDAC cell line (PANC1). We evaluated the ability of the aurora kinase inhibitor CCT137690 to stimulate necroptosis in PDAC cell lines (PANC1, PANC2...
November 2017: Gastroenterology
https://www.readbyqxmd.com/read/28717852/elevated-s100a8-protein-expression-in-breast-cancer-cells-and-breast-tumor-stroma-is-prognostic-of-poor-disease-outcome
#19
P Miller, K M Kidwell, D Thomas, M Sabel, J M Rae, D F Hayes, B I Hudson, D El-Ashry, M E Lippman
PURPOSE: Elevated S100A8 expression has been observed in cancers of the bladder, esophagus, colon, ovary, and breast. S100A8 is expressed by breast cancer cells as well as by infiltrating immune and myeloid cells. Here we investigate the association of elevated S100A8 protein expression in breast cancer cells and in breast tumor stroma with survival outcomes in a cohort of breast cancer patients. PATIENTS AND METHODS: Tissue microarrays (TMA) were constructed from breast cancer specimens from 417 patients with stage I-III breast cancer treated at the University of Michigan Comprehensive Cancer Center between 2004 and 2006...
July 17, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28683472/comprehensive-analysis-of-copy-number-aberrations-in-microsatellite-stable-colon-cancer-in-view-of-stromal-component
#20
M Henar Alonso, Susanna Aussó, Adriana Lopez-Doriga, David Cordero, Elisabet Guinó, Xavier Solé, Mercè Barenys, Javier de Oca, Gabriel Capella, Ramón Salazar, Rebeca Sanz-Pamplona, Victor Moreno
BACKGROUND: Somatic copy number aberrations (CNAs) are common acquired changes in cancer cells having an important role in the progression of colon cancer (colorectal cancer, CRC). This study aimed to perform a characterisation of CNA and their impact in gene expression. METHODS: Copy number aberrations were inferred from SNP array data in a series of 99 CRC. Copy number aberration events were calculated and used to assess the association between copy number dosage, clinical and molecular characteristics of the tumours, and gene expression changes...
July 25, 2017: British Journal of Cancer
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