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immune mediated metastasis

Matthew G K Benesch, Iain T K MacIntyre, Todd P W McMullen, David N Brindley
A quarter-century after the discovery of autotaxin in cell culture, the autotaxin-lysophosphatidate (LPA)-lipid phosphate phosphatase axis is now a promising clinical target for treating chronic inflammatory conditions, mitigating fibrosis progression, and improving the efficacy of existing cancer chemotherapies and radiotherapy. Nearly half of the literature on this axis has been published during the last five years. In cancer biology, LPA signaling is increasingly being recognized as a central mediator of the progression of chronic inflammation in the establishment of a tumor microenvironment which promotes cancer growth, immune evasion, metastasis, and treatment resistance...
March 15, 2018: Cancers
Jessica Wagner, C Leah Kline, Lanlan Zhou, Kerry S Campbell, Alexander W MacFarlane, Anthony J Olszanski, Kathy Q Cai, Harvey H Hensley, Eric A Ross, Marie D Ralff, Andrew Zloza, Charles B Chesson, Jenna H Newman, Howard Kaufman, Joseph R Bertino, Mark N Stein, Wafik El-Deiry
ONC201 is a first-in-class, orally active anti-tumor agent that upregulates cytotoxic TRAIL pathway signaling in cancer cells. ONC201 has demonstrated safety and preliminary efficacy in the first-in-human trial where patients were dosed every 3 weeks. We hypothesized that dose-intensification of ONC201 may impact anti-tumor efficacy. We discovered that ONC201 exerts dose- and schedule-dependent effects on tumor progression and cell-death signaling in vivo. With dose intensification, we note a potent anti-metastasis effect and inhibition of cancer cell migration and invasion...
March 13, 2018: Journal of Clinical Investigation
Jun Li, Hui-Chen Hsu, John D Mountz, John G Allen
Fucosylation is a biological process broadly observed in vertebrates, invertebrates, plants, bacteria, and fungi. Fucose moieties on cell-surface glycans are increasingly recognized as critical to many cell-cell interaction and signaling processes. One of the characteristic roles of fucose is its regulation of selectin-dependent leukocyte adhesion that has been well studied over the last two decades. Recent studies of fucose in immune cell development and function regulation have significantly expanded the contemporary understanding of fucosylation...
February 24, 2018: Cell Chemical Biology
Alexandra Frelau, Marc Pracht, Samuel Le Sourd, Alexandra Lespagnol, Romain Corre, Cédric Ménard, Karin Tarte, Jean Mosser, Julien Edeline
PD-1 checkpoint inhibitors are becoming the reference treatment for several types of cancers. Many patients show remarkable efficacy and low toxicity. However, some patients have a better outcome than others with PD-1 checkpoint inhibitors. So, it is crucial to identify biomarkers of response. We review here the available data of several potential biomarkers of efficacy. The expression of PD-L1, detected by immunohistochemistry on tumor cells and immune cells is a good predictive biomarker of response for some cancers; however, this method is not standardized, and there are different antibodies, different cut-off values, and different targets (tumor or microenvironment)...
March 7, 2018: Bulletin du Cancer
Donata Szymczak, Jarosław Dybko, Kazimierz Kuliczkowski
Hypoxia, understood as low partial oxygen pressure, has become one of the most explored fields in recent years. Cellular response to hypoxia is mediated by hypoxia-inducible factors (HIFs) - potent transcription regulators, and their downstream pathways. In general, HIFs modify energy metabolism, inflammation and immune response, enhance cancer invasion, metastasis, resistance to treatment, and relapse. The influence of HIFs on the progression of leukemia is still under investigation in various studies, but in mice and some human models HIFs have been recognized as leukemia immortalizers by promoting leukemic stem cell quiescence and inhibiting their cell cycle...
February 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Brian A Aguado, Rachel M Hartfield, Grace G Bushnell, Joseph T Decker, Samira M Azarin, Dhaval Nanavati, Matthew J Schipma, Shreyas S Rao, Robert S Oakes, Yining Zhang, Jacqueline S Jeruss, Lonnie D Shea
Primary tumor (PT) immune cells and pre-metastatic niche (PMN) sites are critical to metastasis. Recently, synthetic biomaterial scaffolds used as PMN mimics are shown to capture both immune and metastatic tumor cells. Herein, studies are performed to investigate whether the scaffold-mediated redirection of immune and tumor cells would alter the primary tumor microenvironment (TME). Transcriptomic analysis of PT cells from scaffold-implanted and mock-surgery mice identifies differentially regulated pathways relevant to invasion and metastasis progression...
March 9, 2018: Advanced Healthcare Materials
Xiaohong Ruby Xu, George M Yousef, Heyu Ni
Platelets have long been recognized as key players in hemostasis and thrombosis; however, growing evidence suggests that they are also significantly involved in cancer, the second leading cause of mortality worldwide. Preclinical and clinical studies showed that tumorigenesis and metastasis can be promoted by platelets through a wide variety of crosstalk between platelets and cancer cells. For example, cancer changes platelet behavior by directly inducing tumor-platelet aggregates, triggering platelet granule and extracellular vesicle release, altering platelet phenotype and platelet RNA profiles, and enhancing thrombopoiesis...
March 8, 2018: Blood
C Randall Harrell, Bojana Simovic Markovic, Crissy Fellabaum, Aleksandar Arsenijevic, Valentin Djonov, Vladislav Volarevic
BACKGROUND: Pericytes are multipotent cells present in every vascularized tissue in the body. Despite the fact that they are well-known for more than a century, pericytes are still representing cells with intriguing properties. This is mainly because of their heterogeneity in terms of definition, tissue distribution, origin, phenotype and multi-functional properties. The body of knowledge illustrates importance of pericytes in the regulation of homeostatic and healing processes in the body...
March 9, 2018: Journal of Biomedical Science
Miseon Lee, In Hye Song, Sun-Hee Heo, Young-Ae Kim, In Ah Park, Won Seon Bang, Hye Seon Park, Gyungyub Gong, Hee Jin Lee
Purpose: In the presence of interferon, proteasome subunits are replaced by their inducible counterparts to form an immunoproteasome (IP) plays a key role in generation of antigenic peptides presented by MHC class I molecules, leading to elicitation of a T cell‒mediated immune response. Although the roles of IP in other cancers, and inflammatory diseases have been extensively studied, its significance in breast cancer is unclear. Materials and Methods: We investigated the expression of LMP7, an IP subunit, and its relationship with immune system components in two breast cancer cohorts...
February 26, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Dian Peng, Bin Cao, Ying-Jun Zhou, Ya-Qiu Long
The CXC chemokine receptor 4 (CXCR4) is a highly reserved G-protein coupled 7-transmembrane (TM) chemokine receptor which consists of 352 amino acids. CXCR4 has only one endogenous chemokine ligand of CXCL12, besides several other natural nonchemokine ligands such as extracellular ubiquitin and noncognate ligand of MIF. CXCR4 strongly binds to CXCL12 and the resulting CXCLl2/CXCR4 axis is the molecular basis of their various biological functions, which include: (1) mediating immune and inflammatory response; (2) regulation of hematopoietic stem cell migration and homing; (3) an essential co-receptor for HIV entry into host cells; (4) participation in the process of embryonic development; (5) malignant tumor invasion and metastasis; (6) myocardial infarction, ischemic stroke and acute kidney injury...
February 17, 2018: European Journal of Medicinal Chemistry
Hailin Zhao, Qian Chen, Azeem Alam, Jiang Cui, Ka Chun Suen, Aurelie Pac Soo, Shiori Eguchi, Jianteng Gu, Daqing Ma
Osteopontin (OPN) is a bone sialoprotein involved in osteoclast attachment to mineralised bone matrix, as well as being a bone matrix protein, OPN is also a versatile protein that acts on various receptors which are associated with different signalling pathways implicated in cancer. OPN mediates various biological events involving the immune system and the vascular system; the protein plays a role in processes such as immune response, cell adhesion and migration, and tumorigenesis. This review discusses the potential role of OPN in tumour cell proliferation, angiogenesis and metastasis, as well as the molecular mechanisms involved in these processes in different cancers, including brain, lung, kidney, liver, bladder, breast, oesophageal, gastric, colon, pancreatic, prostate and ovarian cancers...
March 2, 2018: Cell Death & Disease
Wamidh H Talib
Melatonin is a natural indoleamine produced by the pineal gland that has many functions, including regulation of the circadian rhythm. Many studies have reported the anticancer effect of melatonin against a myriad of cancer types. Cancer hallmarks include sustained proliferation, evading growth suppressors, metastasis, replicative immortality, angiogenesis, resisting cell death, altered cellular energetics, and immune evasion. Melatonin anticancer activity is mediated by interfering with various cancer hallmarks...
February 26, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Carlo Sorrentino, Stefania Livia Ciummo, Giuseppe Cipollone, Sara Caputo, Matteo Bellone, Emma Di Carlo
Prostate cancer (PC) stem-like cells (PCSLCs) are believed to be responsible for PC onset and metastasis. Autocrine and microenvironmental signals dictate PCSLC behavior and patient outcome. In PC patients, interleukin(IL)-30/IL-27p28 has been linked with tumor progression, but the mechanisms underlying this link remain mostly elusive. Here we asked whether IL-30 may favor PC progression by conditioning PCSLCs and assessed the value of blocking IL-30 to suppress tumor growth. IL-30 was produced by PCSLCs in human and murine prostatic intraepithelial neoplasia and displayed significant autocrine and paracrine effects...
February 27, 2018: Cancer Research
Nataša Todorović-Raković, Marko Radulovic, Tijana Vujasinović, Jelena Milovanović, Dragica Nikolić-Vukosavljević
There is increasing evidence for the importance of immunity in breast cancer. IFNγ is expected to have a prognostic value based on its major role in innate and specific cell-mediated immunity. In this retrospective study, based on the 14-year follow-up of 73 patients with breast cancer after surgery and radiotherapy but no subsequent systemic therapy, we investigated the prognostic time dependence of intra-tumoural IFNγ mRNA and protein levels. Over the entire 14 years of follow-up, neither IFNγ mRNA nor protein was significantly associated with metastasis outcome by AUC and Cox regression criteria...
November 1, 2017: European Cytokine Network
Alessandra Castegna, Alessio Menga
Glutamine synthetase (GS) is the adenosine triphosphate (ATP)-dependent enzyme that catalyses the synthesis of glutamine by condensing ammonium to glutamate. In the circulatory system, glutamine carries ammonia from muscle and brain to the kidney and liver. In brain reduction of GS activity has been suggested as a mechanism mediating neurotoxicity in neurodegenerative disorders. In cancer, the delicate balance between glutamine synthesis and catabolism is a critical event. In vitro evidence, confirmed in vivo in some cases, suggests that reduced GS activity in cancer cells associates with a more invasive and aggressive phenotype...
February 19, 2018: Genes
Nevena Gajovic, Milena Jurisevic, Jelena Pantic, Gordana D Radosavljevic, Nebojsa Arsenijevic, Miodrag Lukic, Ivan Jovanovic
Diabetic patients have higher incidence and mortality of cancer. Recent study revealed that hyperglycemia-induced oxidative stress is involved in the acceleration of tumor metastasis. We used model of high dose streptozotocin-induced diabetes to investigate its effect on tumor growth and modulation of antitumor immune response of 4T1 murine breast cancer in BALB/c mice. Diabetes accelerated tumor appearance, growth and weight, which was associated with decreased NK cells cytotoxicity against 4T1 tumor cells in vitro...
February 19, 2018: Endocrine-related Cancer
Yaojie Fu, Shanshan Liu, Shan Zeng, Hong Shen
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant diseases worldwide. It is refractory to conventional treatments, and consequently has a documented 5-year survival rate as low as 7%. Increasing evidence indicates that activated pancreatic stellate cells (PSCs), one of the stromal components in tumor microenvironment (TME), play a crucial part in the desmoplasia, carcinogenesis, aggressiveness, metastasis associated with PDAC. Despite the current understanding of PSCs as a "partner in crime" to PDAC, detailed regulatory roles of PSCs and related microenvironment remain obscure...
February 19, 2018: Molecular Cancer
Martin Kolev, Maciej M Markiewski
Complement was initially discovered as an assembly of plasma proteins "complementing" the cytolytic activity of antibodies. However, our current knowledge places this complex system of several plasma proteins, receptors, and regulators in the center of innate immunity as a bridge between the initial innate responses and adaptive immune reactions. Consequently, complement appears to be pivotal for elimination of pathogens, not only as an early response defense, but by directing the subsequent adaptive immune response...
February 14, 2018: Seminars in Immunology
Matteo Massara, Ornella Bonavita, Benedetta Savino, Nicoletta Caronni, Valeria Mollica Poeta, Marina Sironi, Elisa Setten, Camilla Recordati, Laura Crisafulli, Francesca Ficara, Alberto Mantovani, Massimo Locati, Raffaella Bonecchi
Atypical chemokine receptors (ACKRs) are regulators of leukocyte traffic, inflammation, and immunity. ACKR2 is a scavenger for most inflammatory CC chemokines and is a negative regulator of inflammation. Here we report that ACKR2 is expressed in hematopoietic precursors and downregulated during myeloid differentiation. Genetic inactivation of ACKR2 results in increased levels of inflammatory chemokine receptors and release from the bone marrow of neutrophils with increased anti-metastatic activity. In a model of NeuT-driven primary mammary carcinogenesis ACKR2 deficiency is associated with increased primary tumor growth and protection against metastasis...
February 14, 2018: Nature Communications
Iryna Saranchova, Jeffrey Han, Rysa Zaman, Hitesh Arora, Hui Huang, Franz Fenninger, Kyung Bok Choi, Lonna Munro, Cheryl G Pfeifer, Ian Welch, Fumio Takei, Wilfred A Jefferies
Type 2 innate lymphoid cells (ILC2) potentiate immune responses, however, their role in mediating adaptive immunity in cancer has not been assessed. Here, we report that mice genetically lacking ILC2s have significantly increased tumour growth rates and conspicuously higher frequency of circulating tumour cells (CTCs) and resulting metastasis to distal organs. Our data support the model that IL-33 dependent tumour-infiltrating ILC2s are mobilized from the lungs and other tissues through chemoattraction to enter tumours, and subsequently mediate tumour immune-surveillance by cooperating with dendritic cells to promote adaptive cytolytic T cell responses...
February 13, 2018: Scientific Reports
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