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Chi Huu Nguyen, Stefan Brenner, Nicole Huttary, Atanas Georgiev Atanasov, Verena Maria Dirsch, Waranya Chatuphonprasert, Sivio Holzner, Serena Stadler, Juliane Riha, Sigurd Krieger, Rainer de Martin, Zsuzsanna Bago-Horvath, Georg Krupitza, Walter Jäger
A causal link between overexpression of aryl hydrocarbon receptor (AHR) and its target cytochrome P450 1A1 (CYP1A1) and metastatic outgrowth of various cancer entities has been established. Nevertheless, the mechanism how AHR/CYP1A1 support metastasis formation is still little understood. In vitro we discovered a potential mechanism facilitating tumour dissemination based on the production of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE). Utilising a three-dimensional lymph endothelial cell (LEC) monolayer & MDA-MB231 breast cancer cell spheroid co-culture model in combination with knock-down approach allowed elucidation of the molecular/biochemical basis of AHR/CYP1A1-induced tumour breaching through the LEC barrier...
September 27, 2016: Human Molecular Genetics
Weijing Han, Shaohua Chen, Wei Yuan, Qihui Fan, Jianxiang Tian, Xiaochen Wang, Longqing Chen, Xixiang Zhang, Weili Wei, Ruchuan Liu, Junle Qu, Yang Jiao, Robert H Austin, Liyu Liu
In this work, we constructed a Collagen I-Matrigel composite extracellular matrix (ECM). The composite ECM was used to determine the influence of the local collagen fiber orientation on the collective intravasation ability of tumor cells. We found that the local fiber alignment enhanced cell-ECM interactions. Specifically, metastatic MDA-MB-231 breast cancer cells followed the local fiber alignment direction during the intravasation into rigid Matrigel (∼10 mg/mL protein concentration).
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
Felista L Tansi, Ronny Rüger, Claudia Böhm, Roland E Kontermann, Ulf K Teichgraeber, Alfred Fahr, Ingrid Hilger
The underlying data demonstrates that fibroblast activation protein (FAP) paves the way for fibrosarcoma cells, which require the proteolysis of the extracellular matrix (ECM) and basement membranes to intravasate from implanted subcutaneous primary tumors into blood vessels, be transported to distant organs where they extravasate from the blood vessels, reattach and proliferate to metastases. The data additionally shows that FAP, when overexpressed on fibrosarcoma cells induces their invasion and formation of spontaneous metastases in multiple organs, particularly after subcutaneous co-implantation of the FAP-expressing and wildtype fibrosarcoma...
December 2016: Data in Brief
Carmen Viski, Courtney König, Magdalena Kijewska, Carolin Mogler, Clare M Isacke, Hellmut G Augustin
Metastasis is a multistep process that is critically dependent on the interaction of metastasizing tumor cells with cells in the local microenvironment. Within this tumor stroma, vessel-associated pericytes and myofibroblasts share a number of traits, including the upregulated expression of the transmembrane receptor endosialin (CD248). Comparative experiments in wild-type and endosialin-deficient mice revealed that stromal endosialin does not affect primary tumor growth but strongly promotes spontaneous metastasis...
September 15, 2016: Cancer Research
Gabriele Ciasca, Massimiliano Papi, Eleonora Minelli, Valentina Palmieri, Marco De Spirito
Colorectal cancer (CRC) development represents a multistep process starting with specific mutations that affect proto-oncogenes and tumour suppressor genes. These mutations confer a selective growth advantage to colonic epithelial cells that form first dysplastic crypts, and then malignant tumours and metastases. All these steps are accompanied by deep mechanical changes at the cellular and the tissue level. A growing consensus is emerging that such modifications are not merely a by-product of the malignant progression, but they could play a relevant role in the cancer onset and accelerate its progression...
August 28, 2016: World Journal of Gastroenterology: WJG
Lukas Klumpp, Efe C Sezgin, Franziska Eckert, Stephan M Huber
Breast cancer, lung cancer and melanoma exhibit a high metastatic tropism to the brain. Development of brain metastases severely worsens the prognosis of cancer patients and constrains curative treatment options. Metastasizing to the brain by cancer cells can be dissected in consecutive processes including epithelial-mesenchymal transition, evasion from the primary tumor, intravasation and circulation in the blood, extravasation across the blood-brain barrier, formation of metastatic niches, and colonization in the brain...
2016: International Journal of Molecular Sciences
A de Mingo Pulido, B Ruffell
Metastatic disease is the major cause of fatalities in cancer patients, but few therapies are designed to target the metastatic process. Cancer cells must perform a number of steps to successfully establish metastatic foci, including local invasion, intravasation, survival, extravasation, and growth in ectopic tissue. Due to the nonrandom distribution of metastasis, it has long been recognized that the tissue microenvironment must be an important determinant of colonization. More recently it has been established in animal models that immune cells regulate the metastatic process, including a dominant role for monocytes and macrophages, and emerging roles for neutrophils and various lymphocyte populations...
2016: Advances in Cancer Research
Lian Willetts, David Bond, Konstantin Stoletov, John D Lewis
Metastasis, or the spread of cancer cells from a primary tumor to distant sites, is the leading cause of cancer-associated death. Metastasis is a complex multi-step process comprised of invasion, intravasation, survival in circulation, extravasation, and formation of metastatic colonies. Currently, in vitro assays are limited in their ability to investigate these intricate processes and do not faithfully reflect metastasis as it occurs in vivo. Traditional in vivo models of metastasis are limited by their ability to visualize the seemingly sporadic behavior of where and when cancer cells spread (Reymond et al...
2016: Methods in Molecular Biology
Yunlong Yang, Yin Zhang, Hideki Iwamoto, Kayoko Hosaka, Takahiro Seki, Patrik Andersson, Sharon Lim, Carina Fischer, Masaki Nakamura, Mitsuhiko Abe, Renhai Cao, Peter Vilhelm Skov, Fang Chen, Xiaoyun Chen, Yongtian Lu, Guohui Nie, Yihai Cao
The impact of discontinuation of anti-VEGF cancer therapy in promoting cancer metastasis is unknown. Here we show discontinuation of anti-VEGF treatment creates a time-window of profound structural changes of liver sinusoidal vasculatures, exhibiting hyper-permeability and enlarged open-pore sizes of the fenestrated endothelium and loss of VE-cadherin. The drug cessation caused highly leaky hepatic vasculatures permit tumour cell intravasation and extravasation. Discontinuation of an anti-VEGF antibody-based drug and sunitinib markedly promotes liver metastasis...
2016: Nature Communications
Emily J A Telford, Wen G Jiang, Tracey A Martin
Formerly known for its importance in the immune system and kidney regeneration, it is becoming more apparent that HAVcR-1 an important protein in cancer biology. HAVcR-1 is overexpressed in numerous cancers and associates with critical molecules of tight junctions. Tight junctions are critical in homeostasis of cellular compartments via the maintenance of epithelia and endothelia however it has also be suggested that via the prevention of dissemination, intravasation and extravasation, tight junctions play a critical role in the prevention of cancer metastasis...
August 31, 2016: Histology and Histopathology
Stefan Südfeld, Sami R Leyh-Bannurah, Lars Budäus, Markus Graefen, Philip C Reese, Franziska von Breunig, Daniel A Reuter, Bernd Saugel
BACKGROUND: Hydroxyethyl starch (HES) is used for repletion of acute intravasal volume loss in surgical patients. However, in critically ill patients, HES is associated with acute kidney injury. We aimed to evaluate the effect of HES on perioperative cystatin C (cystC)-derived estimated glomerular filtration rates (eGFRcystC) in patients undergoing open and robot-assisted radical prostatectomy. METHODS: In this retrospective study we included 179 patients who underwent general anaesthesia for radical prostatectomy received HES perioperatively, and had complete cystC and fluid therapy data available...
2016: BMC Anesthesiology
Chiara Arrigoni, Simone Bersini, Mara Gilardi, Matteo Moretti
Advanced breast cancer frequently metastasizes to bone through a multistep process involving the detachment of cells from the primary tumor, their intravasation into the bloodstream, adhesion to the endothelium and extravasation into the bone, culminating with the establishment of a vicious cycle causing extensive bone lysis. In recent years, the crosstalk between tumor cells and secondary organs microenvironment is gaining much attention, being indicated as a crucial aspect in all metastatic steps. To investigate the complex interrelation between the tumor and the microenvironment, both in vitro and in vivo models have been exploited...
2016: International Journal of Molecular Sciences
Jongchan Kim, Ashley N Siverly, Dahu Chen, Min Wang, Yuan Yuan, Yumeng Wang, Hyemin Lee, Jinsong Zhang, William J Muller, Han Liang, Boyi Gan, Xianbin Yang, Yutong Sun, M James You, Li Ma
The invasive and metastatic properties of many human tumors have been associated with upregulation of the microRNA miR-10b, but its functional contributions in this setting have not been fully unraveled. Here we report the generation of miR-10b-deficient mice in which miR-10b is shown to be largely dispensable for normal development but critical to tumorigenesis. Loss of miR-10b delays oncogene-induced mammary tumorigenesis and suppresses epithelial-mesenchymal transition, intravasation, and metastasis in a mouse model of metastatic breast cancer...
August 28, 2016: Cancer Research
Rikke Karlin Jepsen, Guy Wayne Novotny, Louise Laurberg Klarskov, Ib Jarle Christensen, Estrid Høgdall, Lene Buhl Riis
INTRODUCTION: miR-21, miR-92a and miR-200c are regulators of pathways involved in migration, intravasation and metastasis, and their tumor expression levels have been proposed as potential prognostic markers in colorectal cancer (CRC). In two parallel cohorts we examine intra-tumor expression levels in early stage CRC tissue in order to determine intra-tumor heterogeneity, potential systematic intra-tumor expression gradients of the miRNAs and to investigate the association to metastatic disease in early stage CRC...
August 23, 2016: Experimental and Molecular Pathology
W Zhou, M G Cao, J Xu, Z Y Fang, X Y Wang, Z P Guo, S S Li, Z H Zhou
OBJECTIVE: To investigate the effect of GTPase activating protein Git2 on metastasis in breast cancer. METHODS: Git2 gene over-expression was induced by Git2 cDNA, and Git2 gene knockdown was induced by Git2 ShRNA lentivirus in four breast cancer cell lines. Six-week old wide type female mice were also used in this study. The cells were tagged with luciferase and injected into wide type female mice by tail vein or 4(th) mammary fat pad, respectively, to establish a cancer metastasis model...
July 2016: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
S Tabariès, P M Siegel
TJs are large intercellular adhesion complexes that maintain cell polarity in normal epithelia and endothelia. During the metastatic process, TJs must be 'loosened' or dismantled in cancer cells to enable migration and dissemination. Diminished TJ integrity must also occur within endothelial cells to allow intravasation and extravasation of cancer cells across endothelial barriers. Claudins are critical components of TJs, forming homo- and heteromeric interactions between the adjacent cells, which have been implicated as key modulators of carcinogenesis and metastasis...
August 15, 2016: Oncogene
Helena J Janse van Rensburg, Xiaolong Yang
Cancer metastasis refers to the sequence of events whereby tumour cells detach from their primary tissue, invade and migrate to nearby vasculature, intravasate into circulation, survive in circulation and extravasate at a distant site to establish a secondary tumour. Each step in this "metastatic cascade" is coordinated by complex molecular events that remain only incompletely understood. Given that the vast majority of cancer fatalities occur due to metastasis, there is an urgent need for an improved understanding of the specific mechanisms underlying cancer metastasis and for the development of therapeutics targeting this lethal process...
November 2016: Cellular Signalling
Virginia Pensabene, Lino Costa, Alexander Y Terekhov, Juan S Gnecco, John P Wikswo, William H Hofmeister
The basal lamina or basement membrane (BM) is a key physiological system that participates in physicochemical signaling between tissue types. Its formation and function are essential in tissue maintenance, growth, angiogenesis, disease progression, and immunology. In vitro models of the BM (e.g., Boyden and transwell chambers) are common in cell biology and lab-on-a-chip devices where cells require apical and basolateral polarization. Extravasation, intravasation, membrane transport of chemokines, cytokines, chemotaxis of cells, and other key functions are routinely studied in these models...
August 31, 2016: ACS Applied Materials & Interfaces
Ching-Min Lin, Yu-Ling Lin, Shu-Yi Ho, Pin-Rong Chen, Yi-Hsuan Tsai, Chen-Han Chung, Chia-Hsiang Hwang, Nu-Man Tsai, Shey-Cherng Tzou, Chun-Yen Ke, Jung Chang, Yi-Lin Chan, Yu-Shan Wang, Kwan-Hwa Chi, Kuang-Wen Liao
7,7"-Dimethoxyagastisflavone (DMGF), a biflavonoid isolated from Taxus x media cv. Hicksii, induces apoptotic and autophagic cell death. However, whether DMGF suppresses tumor metastasis is unclear. The aim of this study was to investigate the anti-metastatic activities of DMGF on the metastatic processes of melanoma cells in vivo and in vitro. A transwell assay showed that DMGF could effectively attenuate the motility of B16F10 cells, and the results of real-time PCR revealed that DMGF also suppressed the expressions of matrix metalloproteinase-2 (MMP-2)...
July 30, 2016: Oncotarget
Chi Huu Nguyen, Stefan Brenner, Nicole Huttary, Yuanfang Li, Atanas Georgiev Atanasov, Verena M Dirsch, Silvio Holzner, Serena Stadler, Juliane Riha, Sigurd Krieger, Danijela Milovanovic, Adryan Fristiohardy, Ingrid Simonitsch-Klupp, Helmut Dolznig, Philipp Saiko, Thomas Szekeres, Benedikt Giessrigl, Walter Jäger, Georg Krupitza
Secretion of 12(S)-HETE by breast cancer emboli provokes "circular chemorepellent induced defects" (CCIDs) in the adjacent lymphatic vasculature facilitating their intravasation and lymph node metastasis which determines prognosis. Therefore, elucidating the mechanism of lymph endothelial cell (LEC) wall disintegration may provide cues for anti-metastatic intervention. The role of intracellular free Ca(2+) for CCID formation was investigated in LECs using MCF-7 or MDA-MB231 breast cancer cell spheroids in a three-dimensional cell co-culture model...
September 28, 2016: Cancer Letters
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