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https://www.readbyqxmd.com/read/29342200/inhibiting-tgf-beta-signaling-preserves-the-function-of-highly-activated-in-vitro-expanded-natural-killer-cells-in-aml-and-colon-cancer-models
#1
Folashade Otegbeye, Evelyn Ojo, Stephen Moreton, Nathan Mackowski, Dean A Lee, Marcos de Lima, David N Wald
Natural killer cells harnessed from healthy individuals can be expanded ex vivo using various platforms to produce large doses for adoptive transfer into cancer patients. During such expansion, NK cells are increasingly activated and more efficient at killing cancer cells. Adoptive transfer however introduces these activated cells into a highly immunosuppressive tumor microenvironment mediated in part by excessive transforming growth factor beta (TGF-beta) from both cancer cells and their surrounding stroma...
2018: PloS One
https://www.readbyqxmd.com/read/29326439/lung-fibroblasts-promote-metastatic-colonization-through-upregulation-of-stearoyl-coa-desaturase-1-in-tumor-cells
#2
Guanghua Liu, Shi Feng, Lin Jia, Chunying Wang, Yan Fu, Yongzhang Luo
As a rate-limiting step in metastasis, metastatic colonization requires survival signals from supportive stroma. However, the mechanisms driving this process are incompletely understood. Here, we showed that the proliferation of B16F10 cells was promoted when cocultured with lung fibroblasts. Meanwhile, co-injection of B16F10 tumor cells with mouse lung fibroblasts significantly increased lung metastasis. Based on GEO database, we identified stearoyl-CoA desaturase 1 (SCD1) as a novel factor promoting metastatic colonization...
January 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29320521/cd8-t-cell-infiltration-in-breast-and-colon-cancer-a-histologic-and-statistical-analysis
#3
James Ziai, Houston N Gilbert, Oded Foreman, Jeffrey Eastham-Anderson, Felix Chu, Mahrukh Huseni, Jeong M Kim
The prevalence of cytotoxic tumor infiltrating lymphocytes (TILs) has demonstrated prognostic value in multiple tumor types. In particular, CD8 counts (in combination with CD3 and CD45RO) have been shown to be superior to traditional UICC staging in colon cancer patients and higher total CD8 counts have been associated with better survival in breast cancer patients. However, immune infiltrate heterogeneity can lead to potentially significant misrepresentations of marker prevalence in routine histologic sections...
2018: PloS One
https://www.readbyqxmd.com/read/29318561/analysis-of-somatic-dna-methylation-alterations-of-genes-encoding-cell-surface-metallopeptidases-in-colorectal-cancer
#4
Sergio Alonso, Beatriz González, Andreu Alibés, Manuel Perucho
The genome of cancer cells accumulates numerous genetic and epigenetic somatic alterations ultimately conferring capabilities for unrestrained growth, invasion of local tissues, migration, and colonization of distant organs. Many of these new capabilities require the disruption of the cell-to-cell interactions between the cancer cell and its microenvironment. These interactions are mediated, among other factors, by the activity of extracellular enzymes that reshape not only the extracellular compartment of the cancer cells but also that of the neighboring non-cancerous stroma cells...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29300388/colonoscopy-based-colorectal-cancer-modeling-in-mice-with-crispr-cas9-genome-editing-and-organoid-transplantation
#5
Jatin Roper, Tuomas Tammela, Adam Akkad, Mohammad Almeqdadi, Sebastian B Santos, Tyler Jacks, Ömer H Yilmaz
Most genetically engineered mouse models (GEMMs) of colorectal cancer are limited by tumor formation in the small intestine, a high tumor burden that limits metastasis, and the need to generate and cross mutant mice. Cell line or organoid transplantation models generally produce tumors in ectopic locations-such as the subcutaneous space, kidney capsule, or cecal wall-that do not reflect the native stromal environment of the colon mucosa. Here, we describe detailed protocols to rapidly and efficiently induce site-directed tumors in the distal colon of mice that are based on colonoscopy-guided mucosal injection...
February 2018: Nature Protocols
https://www.readbyqxmd.com/read/29290958/stromal-annexin-a2-expression-is-predictive-of-decreased-survival-in-pancreatic-cancer
#6
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/29273547/-molecular-characterisation-defines-several-subtypes-of-pancreatic-ductal-adenocarcinoma
#7
REVIEW
Jérôme Raffenne, Jérôme Cros
Multi-omics high throughput analyses lead to the description of multiple molecular subtypes of pancreatic adenocarcinoma with major prognostic impact for most of them. There is no consensual multilevel integrative classification yet like in colon or breast cancers. Genomic classifications have identified a tumor subtype (15% of the patients) with deficient homologous DNA repair-system leading to increase sensitivity to platinum-based therapies and possibly to PARP inhibitors and immunotherapies. Transcriptomic classifications are still debated but all have identified an aggressive subtype with a very poor prognosis, presumably unfit for a surgical approach...
December 19, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29259703/prostaglandin-e2-ep2-signaling-as-a-node-of-chronic-inflammation-in-the-colon-tumor-microenvironment
#8
REVIEW
Tomohiro Aoki, Shuh Narumiya
Background: Colorectal cancer is the third most common cancer. Involvement of prostaglandin (PG) system in the pathogenesis of colorectal cancer has been suggested from clinical studies demonstrating therapeutic effect of NSAIDs including aspirin or selective COX-2 inhibitors. However, mechanisms on how PG regulates inflammatory responses leading to colorectal cancer development remain obscure. Further, careful attention is needed to use these drugs for a long time because of adverse effects due to non-specific inhibition of physiological PG production in addition to pathological one, making the development of alternatives to aspirin important...
2017: Inflammation and Regeneration
https://www.readbyqxmd.com/read/29245949/functional-profiling-of-microtumors-to-identify-cancer-associated-fibroblast-derived-drug-targets
#9
Shane R Horman, Jeremy To, John Lamb, Jocelyn H Zoll, Nicole Leonetti, Buu Tu, Rita Moran, Robbin Newlin, John R Walker, Anthony P Orth
Recent advances in chemotherapeutics highlight the importance of molecularly-targeted perturbagens. Although these therapies typically address dysregulated cancer cell proteins, there are increasing therapeutic modalities that take into consideration cancer cell-extrinsic factors. Targeting components of tumor stroma such as vascular or immune cells has been shown to represent an efficacious approach in cancer treatment. Cancer-associated fibroblasts (CAFs) exemplify an important stromal component that can be exploited in targeted therapeutics, though their employment in drug discovery campaigns has been relatively minimal due to technical logistics in assaying for CAF-tumor interactions...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29242607/the-impact-of-stromal-hic-5-on-the-tumorigenesis-of-colorectal-cancer-through-lysyl-oxidase-induction-and-stromal-remodeling
#10
Tomokatsu Omoto, Joo-Ri Kim-Kaneyama, Xiao-Feng Lei, Akira Orimo, Koji Ohnishi, Kosuke Yoshihara, Aya Miyauchi, Shuo Li, Lin Gao, Takahiro Umemoto, Junichi Tanaka, Kenta Nakahara, Motohiro Takeya, Fumio Ishida, Shin-Ei Kudo, Shogo Haraguchi, Takuro Miyazaki, Akira Miyazaki
Carcinoma-associated fibroblasts (CAFs) influence tumor initiation, progression, and metastasis within the tumor-associated stroma. This suggests that CAFs would be a potential target for tumor therapy. Here we found that Hydrogen peroxide-inducible clone-5 (Hic-5), also named transforming growth factor beta-1-induced transcript 1 protein (Tgfb1i1), was strongly induced in CAFs found in human colorectal cancer. To investigate the role of Hic-5 in CAFs, we isolated CAFs and the control counterpart normal fibroblasts (NFs) from human colorectal cancer and non-cancerous regions, respectively...
December 15, 2017: Oncogene
https://www.readbyqxmd.com/read/29163806/interferon-inducible-cxc-chemokines-are-crucial-immune-modulators-and-survival-predictors-in-colorectal-cancer
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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...
February 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28940664/a-novel-histological-examination-with-dynamic-three-dimensional-reconstruction-from-multiple-immunohistochemically-stained-sections-of-a-pd-l1-positive-colon-cancer
#18
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 microsatellite instability-high (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 by 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; immunohistochemical analysis of PD-L1, CD8, D2-40 and CD31 was performed...
September 21, 2017: Histopathology
https://www.readbyqxmd.com/read/28931753/ask1-dependent-endothelial-cell-activation-is-critical-in-ovarian-cancer-growth-and-metastasis
#19
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
#20
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
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