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https://www.readbyqxmd.com/read/28102193/tumour-derived-interleukin-35-promotes-pancreatic-ductal-adenocarcinoma-cell-extravasation-and-metastasis-by-inducing-icam1-expression
#1
Chongbiao Huang, Na Li, Zengxun Li, Antao Chang, Yanan Chen, Tiansuo Zhao, Yang Li, Xiuchao Wang, Wei Zhang, Zhimin Wang, Lin Luo, Jingjing Shi, Shengyu Yang, He Ren, Jihui Hao
Interleukin 35 (IL-35) is a novel member of the IL-12 family, consisting of an EBV-induced gene 3 (EBI3) subunit and a P35 subunit. IL-35 is an immune-suppressive cytokine mainly produced by regulatory T cells. However, the role of IL-35 in cancer metastasis and progression is not well understood. Here we demonstrate that IL-35 is overexpressed in human pancreatic ductal adenocarcinoma (PDAC) tissues, and that IL-35 overexpression is associated with poor prognosis in PDAC patients. IL-35 has critical roles in PDAC cell extravasation and metastasis by facilitating the adhesion to endothelial cells and transendothelial extravasation...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28096505/the-neuropilin-2-isoform-nrp2b-uniquely-supports-tgf%C3%AE-mediated-progression-in-lung-cancer
#2
Robert M Gemmill, Patrick Nasarre, Joyce Nair-Menon, Federico Cappuzzo, Lorenza Landi, Armida D'Incecco, Hidetaka Uramoto, Takeshi Yoshida, Eric B Haura, Kent Armeson, Harry A Drabkin
Neuropilins (NRP1 and NRP2) are co-receptors for heparin-binding growth factors and class 3 semaphorins. Different isoforms of NRP1 and NRP2 are produced by alternative splicing. We found that in non-small cell lung cancer (NSCLC) cell lines, transforming growth factor-β (TGFβ) signaling preferentially increased the abundance of NRP2b. NRP2b and NRP2a differ only in their carboxyl-terminal regions. Although the presence of NRP2b inhibited cultured cell proliferation and primary tumor growth, NRP2b enhanced cellular migration, invasion into Matrigel, and tumorsphere formation in cultured cells in response to TGFβ signaling and promoted metastasis in xenograft mouse models...
January 17, 2017: Science Signaling
https://www.readbyqxmd.com/read/28089340/activation-of-nk-cell-cytotoxicity-by-aerosolized-cpg-odn-poly-i-c-against-lung-melanoma-metastases-is-mediated-by-alveolar-macrophages
#3
Michele Sommariva, Valentino Le Noci, Chiara Storti, Francesca Bianchi, Elda Tagliabue, Andrea Balsari, Lucia Sfondrini
Controversies remain about NK cells direct responsiveness to Toll-like receptor (TLR) agonists or dependence on macrophages. In a melanoma lung metastasis model, aerosolized TLR9 and TLR3 agonists have been reported to induce antitumor immunity through NK cells activation. In the current study, we demonstrated that in vitro TLR9/TLR3 stimulation induced IFN-γ secretion by NK cells, but an increase in their cytotoxicity was detected only after NK cells co-culture with in vitro TLR9/TLR3 agonists pretreated alveolar macrophages...
January 5, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28081468/role-of-mir-15a-in-intervertebral-disc-degeneration-through-targeting-map3k9
#4
Ping Cai, Ting Yang, Xingjie Jiang, Minghui Zheng, Gang Xu, Jianlong Xia
BACKGROUND: Accumulating evidence indicates that microRNAs are involved in various cellular processes, including cell proliferation, differentiation, apoptosis and metastasis. miR-15a is an important regulator of immune responses and angiogenesis, endogenous controls as well as potential targets and hallmarks of cancer. However, the role of miR-15a in intervertebral disc degeneration (IDD) has not been elucidated. METHODS: Total RNA was extracted from degenerative nucleus pulposus (NP) tissues of 20 patients with IDD and NP cells, respectively...
January 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28077296/extracellular-vesicle-communication-pathways-as-regulatory-targets-of-oncogenic-transformation
#5
REVIEW
Dongsic Choi, Tae Hoon Lee, Cristiana Spinelli, Shilpa Chennakrishnaiah, Esterina D'Asti, Janusz Rak
Pathogenesis of human cancers bridges intracellular oncogenic driver events and their impact on intercellular communication. Among multiple mediators of this 'pathological connectivity' the role of extracellular vesicles (EVs) and their subsets (exosomes, ectosomes, oncosomes) is of particular interest for several reasons. The release of EVs from cancer cells represents a unique mechanism of regulated expulsion of bioactive molecules, a process that also mediates cell-to-cell transfer of lipids, proteins, and nucleic acids...
January 8, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28077173/is-cd47-an-innate-immune-checkpoint-for-tumor-evasion
#6
REVIEW
Xiaojuan Liu, Hyunwoo Kwon, Zihai Li, Yang-Xin Fu
Cluster of differentiation 47 (CD47) (also known as integrin-associated protein) is a ubiquitously expressed glycoprotein of the immunoglobulin superfamily that plays a critical role in self-recognition. Various solid and hematologic cancers exploit CD47 expression in order to evade immunological eradication, and its overexpression is clinically correlated with poor prognoses. One essential mechanism behind CD47-mediated immune evasion is that it can interact with signal regulatory protein-alpha (SIRPα) expressed on myeloid cells, causing phosphorylation of the SIRPα cytoplasmic immunoreceptor tyrosine-based inhibition motifs and recruitment of Src homology 2 domain-containing tyrosine phosphatases to ultimately result in delivering an anti-phagocytic-"don't eat me"-signal...
January 11, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28075526/cetuximab-strongly-enhances-immune-cell-infiltration-into-liver-metastatic-sites-in-colorectal-cancer
#7
Yuka Inoue, Shoichi Hazama, Nobuaki Suzuki, Yukio Tokumitsu, Shinsuke Kanekiyo, Shinobu Tomochika, Ryouichi Tsunedomi, Yoshihiro Tokuhisa, Michihisa Iida, Kazuhiko Sakamoto, Shigeru Takeda, Tomio Ueno, Shigefumi Yoshino, Hiroaki Nagano
Cetuximab has activity against colorectal cancers. Recent studies demonstrated that cetuximab induces antibody-dependent cell-mediated cytotoxicity via immune cells, and a new immune-related mechanism of inducing immunogenic cell death. This study aimed to evaluate the immune responses induced by cetuximab in tumor microenvironments at liver metastasis sites of metastatic colorectal cancer patients. We assessed immune cell infiltration in the liver metastatic sites of 53 colorectal cancer patients. These patients were divided into three groups according to the treatment before operation: chemotherapy with cetuximab, chemotherapy without cetuximab, and no chemotherapy...
January 11, 2017: Cancer Science
https://www.readbyqxmd.com/read/28072716/pneumonitis-in-cancer-patients-receiving-anti-pd-1-and-radiotherapies-three-case-reports
#8
Chieh-Sheng Lu, Jin-Hwang Liu
INTRODUCTION: In development of novel therapies for the treatment of patient with cancer, the use of radiotherapy (RT) can produce significant local control and, in recent studies, has also been shown to mediate anti-tumor responses at distant sites by triggering and enhancing the endogenous cellular immune responses. Although RT induces an abscopal effect in some patients due to enhanced immune response to the tumor, immune-escape mechanisms, including up-regulation of programmed death-ligand 1 (PD-L1) on tumor cells, limit this benefit in other patients...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28067794/the-tgf-%C3%AE-smad4-signaling-pathway-in-pancreatic-carcinogenesis-and-its-clinical-significance
#9
REVIEW
Sunjida Ahmed, Azore-Dee Bradshaw, Shweta Gera, M Zahidunnabi Dewan, Ruliang Xu
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal human cancers due to its complicated genomic instability. PDAC frequently presents at an advanced stage with extensive metastasis, which portends a poor prognosis. The known risk factors associated with PDAC include advanced age, smoking, long-standing chronic pancreatitis, obesity, and diabetes. Its association with genomic and somatic mutations is the most important factor for its aggressiveness. The most common gene mutations associated with PDAC include KRas2, p16, TP53, and Smad4...
January 5, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28061481/b7-h4-promotes-tumor-growth-and-metastatic-progression-in-lung-cancer-by-impacting-cell-proliferation-and-survival
#10
Xiuqin Zhang, Liming Cai, Guangbo Zhang, Yu Shen, Jianan Huang
Aberrant expression of B7-H4 occurs across a broad spectrum of human cancers. The aim of this study was to investigate the key role of B7-H4 during tumorigenesis and metastasis of human lung cancer. Our data showed that the shRNA-mediated disruption of B7-H4 markedly inhibited tumor cell proliferation, invasion and migration, increased cell apoptosis and arrested cell cycle at G0/G1. These changes were accompanied by a marked increase in Bax and caspase-3/caspase-8, but a decrease in Bcl-2, cyclinD1 and activation of AKT...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28055016/inhibition-of-stat3-signaling-pathway-by-nifuroxazide-improves-antitumor-immunity-and-impairs-colorectal-carcinoma-metastasis
#11
Ting-Hong Ye, Fang-Fang Yang, Yong-Xia Zhu, Ya-Li Li, Qian Lei, Xue-Jiao Song, Yong Xia, Ying Xiong, Li-Dan Zhang, Ning-Yu Wang, Li-Feng Zhao, Hong-Feng Gou, Yong-Mei Xie, Sheng-Yong Yang, Luo-Ting Yu, Li Yang, Yu-Quan Wei
Colorectal carcinoma (CRC) is the one of the most common cancers with considerable metastatic potential, explaining the need for new drug candidates that inhibit tumor metastasis. The signal transducers and activators of the transcription 3 (Stat3) signaling pathway has an important role in CRC and has been validated as a promising anticancer target for CRC therapy. In the present study, we report our findings on nifuroxazide, an antidiarrheal agent identified as an inhibitor of Stat3. Our studies showed that nifuroxazide decreased the viability of three CRC cell lines and induced apoptosis of cancer cells in a concentration-dependent manner...
January 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28052056/genome-wide-in-vivo-screen-identifies-novel-host-regulators-of-metastatic-colonization
#12
Louise van der Weyden, Mark J Arends, Andrew D Campbell, Tobias Bald, Hannah Wardle-Jones, Nicola Griggs, Martin Del Castillo Velasco-Herrera, Thomas Tüting, Owen J Sansom, Natasha A Karp, Simon Clare, Diane Gleeson, Edward Ryder, Antonella Galli, Elizabeth Tuck, Emma L Cambridge, Thierry Voet, Iain C Macaulay, Kim Wong, Sanger Mouse Genetics Project, Sarah Spiegel, Anneliese O Speak, David J Adams
Metastasis is the leading cause of death for cancer patients. This multi-stage process requires tumour cells to survive in the circulation, extravasate at distant sites, then proliferate; it involves contributions from both the tumour cell and tumour microenvironment ('host', which includes stromal cells and the immune system). Studies suggest the early steps of the metastatic process are relatively efficient, with the post-extravasation regulation of tumour growth ('colonization') being critical in determining metastatic outcome...
January 4, 2017: Nature
https://www.readbyqxmd.com/read/28049847/gpr132-sensing-of-lactate-mediates-tumor-macrophage-interplay-to-promote-breast-cancer-metastasis
#13
Peiwen Chen, Hao Zuo, Hu Xiong, Matthew J Kolar, Qian Chu, Alan Saghatelian, Daniel J Siegwart, Yihong Wan
Macrophages are prominent immune cells in the tumor microenvironment that exert potent effects on cancer metastasis. However, the signals and receivers for the tumor-macrophage communication remain enigmatic. Here, we show that G protein-coupled receptor 132 (Gpr132) functions as a key macrophage sensor of the rising lactate in the acidic tumor milieu to mediate the reciprocal interaction between cancer cells and macrophages during breast cancer metastasis. Lactate activates macrophage Gpr132 to promote the alternatively activated macrophage (M2)-like phenotype, which, in turn, facilitates cancer cell adhesion, migration, and invasion...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28047031/th-ef-207a-06-high-resolution-optical-ct-ect-imaging-of-unstained-mice-femur-brain-spleen-and-tumor
#14
S Yoon, M Boss, S Birer, M Dewhirst, M Oldham
PURPOSE: Optical transmission and emission computed tomography (optical-CT/ECT) provides high-resolution 3D attenuation and emission maps in unsectioned large (∼1cm(3) ) ex vivo tissue samples at a resolution of 12.9µm(3) per voxel. Here we apply optical-CT/ECT to investigate high-resolution structure and auto-fluorescence in a range of optically cleared mice organs, including, for the first time, mouse bone (femur), opening the potential for study of bone metastasis and bone-mediated immune response...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28035413/tim-3-is-upregulated-in-human-colorectal-carcinoma-and-associated-with-tumor-progression
#15
Muming Yu, Bin Lu, Yancun Liu, Ying Me, Lijun Wang, Peng Zhang
T cell immunoglobulin mucin-3 (Tim-3) has previously been implicated in the immune response and tumor biology. Colorectal carcinoma (CRC) is a malignancy, which is closely associated with inflammation. However, the role of Tim‑3 in the progression of CRC remains to be fully elucidated. The present study aimed to investigate the role of Tim‑3 in the progressive activities of human CRC. A total of 30 clinical CRC tissues and their adjacent tissues were collected. Slides from another 112 cases that underwent CRC surgical resection were also obtained...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28027646/protein-nanocage-mediated-fibroblast-activation-protein-targeted-photoimmunotherapy-to-enhance-cytotoxic-t-cell-infiltration-and-tumor-control
#16
Zipeng Zhen, Wei Tang, Mengzhe Wang, Shiyi Zhou, Hui Wang, Zhanhong Wu, Zhonglin Hao, Zibo Li, Lin Liu, Jin Xie
Carcinoma-associated fibroblasts (CAFs) are found in many types of cancer and play an important role in tumor growth and metastasis. Fibroblast-activation protein (FAP), which is overexpressed on the surface of CAFs, has been proposed as a universal tumor targeting antigen. However, recent studies show that FAP is also expressed on multipotent bone marrow stem cells. A systematic anti-FAP therapy may lead to severe side effects and even death. Hence, there is an urgent need of a therapy that can selectively kill CAFs without causing systemic toxicity...
January 4, 2017: Nano Letters
https://www.readbyqxmd.com/read/27976881/photodynamic-therapy-mediated-by-nontoxic-core-shell-nanoparticles-synergizes-with-immune-checkpoint-blockade-to-elicit-antitumor-immunity-and-antimetastatic-effect-on-breast-cancer
#17
Xiaopin Duan, Christina Chan, Nining Guo, Wenbo Han, Ralph R Weichselbaum, Wenbin Lin
An effective, nontoxic, tumor-specific immunotherapy is the ultimate goal in the battle against cancer, especially the metastatic disease. Checkpoint blockade-based immunotherapies have been shown to be extraordinarily effective but benefit only the minority of patients whose tumors have been pre-infiltrated by T cells. Here, we show that Zn-pyrophosphate (ZnP) nanoparticles loaded with the photosensitizer pyrolipid (ZnP@pyro) can kill tumor cells upon irradiation with light directly by inducing apoptosis and/or necrosis and indirectly by disrupting tumor vasculature and increasing tumor immunogenicity...
December 28, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27974826/aechl-1-targets-breast-cancer-progression-via-inhibition-of-metastasis-prevention-of-emt-and-suppression-of-cancer-stem-cell-characteristics
#18
Aparajita Dasgupta, Mithila A Sawant, Gayatri Kavishwar, Manish Lavhale, Sandhya Sitasawad
Triple negative breast cancer (TNBC) features among the most aggressive manifestations of cancer due to its enhanced metastatic potential and immunity to therapeutics which target hormone receptors. Under such scenarios, anti-cancer compounds with an ability to influence multiple targets, or an entire process, will have an advantage over specific signal transduction inhibitors. To counter the metastatic threat it is essential to target cellular components central to the processes of cancer cell migration and adaptation...
December 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27956175/tumor-promoting-effect-of-il-23-in-mammary-cancer-mediated-by-infiltration-of-m2-macrophages-and-neutrophils-in-tumor-microenvironment
#19
Wen Nie, Ting Yu, Yaxiong Sang, Xiang Gao
Interleukin 23 (IL-23) is an inflammatory cytokine which plays a vital role in autoimmune diseases as well as in tumorigenesis. However, the role of IL-23 in tumor procession is still controversial and the underlying mechanism remains unclear. Here we established a stable cell line overexpressing IL-23 to prove that IL-23 promoted tumor growth and pulmonary metastasis through induction of tumor-related inflammation and absence of immune surveillance. IL-23 promotes tumor-associate inflammatory response such as infiltration of M2 macrophages, neutrophils and their elevated secretions of immunosuppressive cytokines transforming growth factor-β (TGF-β), IL-10 and vascular endothelial growth factor (VEGF) into tumor tissues, meanwhile the increase of the matrix metalloprotease MMP9...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27942419/immune-suppression-mediated-by-myeloid-and-lymphoid-derived-immune-cells-in-the-tumor-microenvironment-facilitates-progression-of-thyroid-cancers-driven-by-hras-g12v-and-pten-loss
#20
Lee Ann Jolly, Nicole Massoll, Aime T Franco
Thyroid cancer is the most common endocrine malignancy and is predicted to be the 4(th) most commonly diagnosed cancer by 2030. Approximately one-half of follicular thyroid carcinomas (FTC) contain genetic alterations in RAS family members. Furthermore, Cowden's disease, which is characterized by loss of PTEN, predisposes for the development of FTC in humans. We have shown that thyroid specific expression of Hras(G12V) at endogenous levels and Pten inactivation (Hras(G12V)/Pten(-/-)/TPO-cre mice) leads to the development of FTCs that closely recapitulate human disease, with complete penetrance at one year...
October 2016: Journal of Clinical & Cellular Immunology
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