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https://www.readbyqxmd.com/read/28618402/epithelial-to-mesenchymal-transition-circulating-tumor-cells-and-cancer-metastasis-mechanisms-and-clinical-applications
#1
REVIEW
Xiao-Xiang Jie, Xiao-Yan Zhang, Cong-Jian Xu
Epithelial-to-mesenchymal transition (EMT) endows epithelial cells with enhanced motility and invasiveness, allowing them to participate in many physiological and pathological processes. Epithelial-to-mesenchymal transition contributes to the generation of circulating tumor cells (CTCs) in epithelial cancers because it increases tumor cell invasiveness, promotes tumor cell intravasation and ensures tumor cell survival in the peripheral system. Although the contribution of epithelial-to-mesenchymal transition to tumor cell invasiveness has been confirmed, the role epithelial-to-mesenchymal transition plays in metastasis remains debated...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28604765/mlk3-regulates-fra-1-and-mmps-to-drive-invasion-and-transendothelial-migration-in-triple-negative-breast-cancer-cells
#2
C Rattanasinchai, B J Llewellyn, S E Conrad, K A Gallo
Mixed-lineage kinase 3 (MLK3), a mitogen-activated protein kinase kinase kinase (MAP3K), has critical roles in metastasis of triple-negative breast cancer (TNBC), in part by regulating paxillin phosphorylation and focal adhesion turnover. However the mechanisms and the distinct step(s) of the metastatic processes through which MLK3 exerts its influence are not fully understood. Here we report that in non-metastatic, estrogen receptor-positive breast cancer (ER+ BC) cells, induced MLK3 expression robustly upregulates the oncogenic transcription factor, FOS-related antigen-1 (FRA-1), which is accompanied by elevation of matrix metalloproteinases (MMPs), MMP-1 and MMP-9...
June 12, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28560677/mesenchymal-epithelial-transition-and-circulating-tumor-cells-in-small-cell-lung-cancer
#3
Gerhard Hamilton, Barbara Rath
Cancer patients die of metastatic disease but knowledge regarding individual steps of this complex process of intravasation, spread and extravasation leading to secondary lesions is incomplete. Subpopulations of tumor cells are supposed to undergo an epithelial-mesenchymal transition (EMT), to enter the bloodstream and eventually establish metastases in a reverse process termed mesenchymal-epithelial transition (MET). Small cell lung cancer (SCLC) represents a unique model to study metastatic spread due to early dissemination and relapse, as well as availability of a panel of circulating cancer cell (CTC) lines recently...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28544498/cancer-metastasis-through-the-prism-of-epithelial-to-mesenchymal-transition-in-circulating-tumor-cells
#4
REVIEW
Douglas S Micalizzi, Daniel A Haber, Shyamala Maheswaran
Metastasis of epithelial cancer cells to distal sites is a particularly critical stage of cancer progression that typically marks the incurability of the disease. It is governed by a complex series of events including invasion and intravasation of tumor cells into the stroma and blood, respectively. Epithelial to mesenchymal transition (EMT), a phenotypic change marked by the loss of epithelial characteristics and the acquisition of invasive mesenchymal properties, is implicated in the dissemination of tumor cells...
May 24, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28538086/sphingosine-1-phosphate-receptor-1-agonist-sew2871-causes-severe-cardiac-side-effects-and-does-not-improve-microvascular-barrier-breakdown-in-sepsis
#5
Sven Flemming, Natalie Burkard, Michael Meir, Martin Alexander Schick, Christoph-Thomas Germer, Nicolas Schlegel
BACKGROUND: Endothelial barrier dysfunction is a hallmark in the pathogenesis of sepsis. Sphingosine-1-phosphate (S1P) has been proposed to be critically involved in the maintenance of endothelial barrier function predominately by activating S1P receptor-1 (S1P1). Previous studies have shown that the specific S1P1 agonist SEW2871 improves endothelial barrier function under inflammatory conditions. However, the effectiveness of SEW2871 and potential side effects remained largely unexplored in a clinically relevant model of sepsis...
May 23, 2017: Shock
https://www.readbyqxmd.com/read/28534212/breast-cancer-metastasis-putative-therapeutic-role-of-vascular-cell-adhesion-molecule-1
#6
REVIEW
Rohit Sharma, Rohini Sharma, Tejinder Pal Khaket, Chanchala Dutta, Bornisha Chakraborty, Tapan Kumar Mukherjee
BACKGROUND: Breast cancer is a notable cause of cancer-related death in women worldwide. Metastasis to distant organs is responsible for ~90% of this death. Breast cells convert to malignant cancer cells after acquiring the capacity of invasion/intravasation into surrounding tissues and, finally, extravasation/metastasis to distant organs (i.e., lymph nodes, lungs, bone, brain). Metastasis to distant organs depends on interactions between disseminated tumor cells (DTCs) and the endothelium of blood vessels present in the tumor microenvironment...
May 22, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28518096/invasive-behavior-of-human-breast-cancer-cells-in-embryonic-zebrafish
#7
Jiang Ren, Sijia Liu, Chao Cui, Peter Ten Dijke
In many cases, cancer patients do not die of a primary tumor, but rather because of metastasis. Although numerous rodent models are available for studying cancer metastasis in vivo, other efficient, reliable, low-cost models are needed to quickly access the potential effects of (epi)genetic changes or pharmacological compounds. As such, we illustrate and explain the feasibility of xenograft models using human breast cancer cells injected into zebrafish embryos to support this goal. Under the microscope, fluorescent proteins or chemically labeled human breast cancer cells are transplanted into transgenic zebrafish embryos, Tg (fli:EGFP), at the perivitelline space or duct of Cuvier (Doc) 48 h after fertilization...
April 25, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28496326/gold-nanoparticles-attenuate-metastasis-by-tumor-vasculature-normalization-and-epithelial-mesenchymal-transition-inhibition
#8
Wei Li, Xin Li, Shuhao Liu, Wende Yang, Fan Pan, Xiao-Yan Yang, Bin Du, Li Qin, Yunlong Pan
Angiogenesis is a process by which vessels are formed through preexisting ones, and this plays a key role in the progression of solid tumors. However, tumor vessels are influenced by excessive pro-angiogenic factors, resulting in deformed structures that facilitate the intravasation of tumor cells into the circulation and subsequent metastasis. Moreover, abnormal tumor vessels have low blood perfusion and thereby decreased oxygen infusion into tumors. This results in a hostile microenvironment that promotes epithelial-mesenchymal transition (EMT), a process in which epithelial cells lose their polarity and gain increased motility, which is associated with metastasis and invasion...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28467903/locally-triggered-release-of-the-chemokine-ccl21-promotes-dendritic-cell-transmigration-across-lymphatic-endothelia
#9
Kari Vaahtomeri, Markus Brown, Robert Hauschild, Ingrid De Vries, Alexander Franz Leithner, Matthias Mehling, Walter Anton Kaufmann, Michael Sixt
Trafficking cells frequently transmigrate through epithelial and endothelial monolayers. How monolayers cooperate with the penetrating cells to support their transit is poorly understood. We studied dendritic cell (DC) entry into lymphatic capillaries as a model system for transendothelial migration. We find that the chemokine CCL21, which is the decisive guidance cue for intravasation, mainly localizes in the trans-Golgi network and intracellular vesicles of lymphatic endothelial cells. Upon DC transmigration, these Golgi deposits disperse and CCL21 becomes extracellularly enriched at the sites of endothelial cell-cell junctions...
May 2, 2017: Cell Reports
https://www.readbyqxmd.com/read/28426929/exerting-enhanced-permeability-and-retention-effect-driven-delivery-by-ultrafine-iron-oxide-nanoparticles-with-t1-t2-switchable-magnetic-resonance-imaging-contrast
#10
Liya Wang, Jing Huang, Hongbo Chen, Hui Wu, Yaolin Xu, Yuancheng Li, Hong Yi, Yongqiang A Wang, Lily Yang, Hui Mao
Poor delivery efficiency remains a major challenge in nanomaterial-based tumor-targeted imaging and drug delivery. This work demonstrates a strategy to improve nanoparticle delivery and intratumoral distribution using sub-5 nm (3.5 nm core size) ultrafine iron oxide nanoparticles (uIONP) that can easily extravasate from the tumor vasculature and readily diffuse into the tumor tissue compared to the iron oxide nanoparticle (IONP) with larger sizes, followed by self-assembling in the acidic tumor interstitial space to limit their re-entering into circulation...
May 23, 2017: ACS Nano
https://www.readbyqxmd.com/read/28423322/intratumoral-cancer-cell-intravasation-can-occur-independent-of-invasion-into-the-adjacent-stroma
#11
Elena I Deryugina, William B Kiosses
Intravasation, active entry of cancer cells into the circulation, is often considered to be a relatively late event in tumor development occurring after stromal invasion. Here, we provide evidence that intravasation can be initiated early during tumor development and proceed in parallel to or independent of tumor invasion into surrounding stroma. By applying direct and unbiased intravasation-scoring methods to two histologically distinct human cancer types in live-animal models, we demonstrate that intravasation takes place almost exclusively within the tumor core, involves intratumoral vasculature, and does not involve vasculotropic cancer cells invading tumor-adjacent stroma and migrating along tumor-converging blood vessels...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28417005/reversibility-of-vasalgel%C3%A2-male-contraceptive-in-a-rabbit-model
#12
Donald Waller, David Bolick, Elaine Lissner, Christopher Premanandan, Gary Gamerman
BACKGROUND: Development of a non-hormonal long-acting reversible contraceptive for men could have a significant impact on reducing unintended pregnancies. Vasalgel™ is a high molecular weight polymer consisting of styrene-alt-maleic acid (SMA) dissolved in dimethyl sulfoxide being developed as a reversible male contraceptive device. It forms a hydrogel when implanted into the vasa deferentia, which prevents the passage of sperm. Previous studies in the rabbit have proven its efficacy, durability and rapid onset...
2017: Basic and Clinical Andrology
https://www.readbyqxmd.com/read/28410495/local-induction-of-lymphangiogenesis-with-engineered-fibrin-binding-vegf-c-promotes-wound-healing-by-increasing-immune-cell-trafficking-and-matrix-remodeling
#13
Esra Güç, Priscilla S Briquez, Didier Foretay, Manuel A Fankhauser, Jeffrey A Hubbell, Witold W Kilarski, Melody A Swartz
Lymphangiogenesis occurs in inflammation and wound healing, yet its functional roles in these processes are not fully understood. Consequently, clinically relevant strategies for therapeutic lymphangiogenesis remain underdeveloped, particularly using growth factors. To achieve controlled, local capillary lymphangiogenesis with protein engineering and determine its effects on fluid clearance, leukocyte trafficking, and wound healing, we developed a fibrin-binding variant of vascular endothelial growth factor C (FB-VEGF-C) that is slowly released upon demand from infiltrating cells...
July 2017: Biomaterials
https://www.readbyqxmd.com/read/28408152/cellular-determinants-and-microenvironmental-regulation-of-prostate-cancer-metastasis
#14
REVIEW
Kiera Rycaj, Hangwen Li, Jianjun Zhou, Xin Chen, Dean G Tang
Metastasis causes more than 90% of cancer-related deaths and most prostate cancer (PCa) patients also die from metastasis. The 'metastatic cascade' is a complex biological process that encompasses tumor cell dissociation (from the primary tumor), local invasion, intravasation, transport in circulation, extravasation, colonization, and overt growth in end organs. It has become clear that successful metastasis not only involves many tumor cell-intrinsic properties but also depends on productive interactions between cancer cells and the tumor microenvironment...
April 11, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28393180/fenofibrate-inhibits-tumour-intravasation-by-several-independent-mechanisms-in-a-3-dimensional-co-culture-model
#15
Chi Huu Nguyen, Nicole Huttary, Atanas G Atanasov, Waranya Chatuphonprasert, Stefan Brenner, Adryan Fristiohady, Junli Hong, Serena Stadler, Silvio Holzner, Daniela Milovanovic, Verena M Dirsch, Brigitte Kopp, Philipp Saiko, Liselotte Krenn, Walter Jäger, Georg Krupitza
Lymph node metastasis of breast cancer is a clinical marker of poor prognosis. Yet, there exist no therapies targeting mechanisms of intravasation into lymphatics. Herein we report on an effect of the antidyslipidemic drug fenofibrate with vasoprotective activity, which attenuates breast cancer intravasation in vitro, and describe the potential mechanisms. To measure intravasation in a 3-dimensional co-culture model MDA-MB231 and MCF-7 breast cancer spheroids were placed on immortalised lymphendothelial cell (LEC) monolayers...
April 7, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28371195/intratumoral-bidirectional-transitions-between-epithelial-and-mesenchymal-cells-in-triple-negative-breast-cancer
#16
Mizuki Yamamoto, Kota Sakane, Kana Tominaga, Noriko Gotoh, Takayoshi Niwa, Yasuko Kikuchi, Keiichiro Tada, Naoki Goshima, Kentaro Semba, Jun-Ichiro Inoue
Epithelial-mesenchymal transition (EMT) and its reverse process, mesenchymal-epithelial transition MET, are crucial in several stages of cancer metastasis. Epithelial-mesenchymal transition allows cancer cells to move to proximal blood vessels for intravasation. However, because EMT and MET processes are dynamic, mesenchymal cancer cells are likely to undergo MET transiently and subsequently re-undergo EMT to restart the metastatic process. Therefore, spatiotemporally coordinated mutual regulation between EMT and MET could occur during metastasis...
April 1, 2017: Cancer Science
https://www.readbyqxmd.com/read/28361934/tumour-blood-vessel-normalisation-by-prolyl-hydroxylase-inhibitor-repaired-sensitivity-to-chemotherapy-in-a-tumour-mouse-model
#17
Satoshi Koyama, Shinji Matsunaga, Masaki Imanishi, Yoichi Maekawa, Hiroya Kitano, Hiromi Takeuchi, Shuhei Tomita
Blood vessels are important tissue structures that deliver oxygen and nutrition. In tumour tissue, abnormal blood vessels, which are hyperpermeable and immature, are often formed; these tissues also have irregular vascularisation and intravasation. This situation leads to hypoperfusion in tumour tissue along with low oxygen and nutrition depletion; this is also called the tumour microenvironment and is characterised by hypoxia, depleted nutrition, low pH and high interstitial pressure. This environment induces resistance to anticancer drugs, which causes an increase in anticancer drug doses, leading to increased side effects...
March 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345239/the-anatomy-of-the-blood-vascular-system-of-the-giant-vestimentiferan-tubeworm-riftia-pachyptila-siboglinidae-annelida
#18
Nadezhda N Rimskaya-Korsakova, Sergey V Galkin, Vladimir V Malakhov
The giant dimensions of vestimentiferan Riftia pachyptila (Jones, ) are achieved thanks to the well-developed vascular system. In the vestimentum, there is a complicated net of lacunae, including the brain blood supply and the ventral lacuna underlying the ciliary field. The trunk region has an extensive network of blood vessels feeding the gonads («rete mirabile»). The thick muscular lining of the mesenterial vessels in the trunk and the dorsal vessel in the opisthosome serves as an additional pump, pushing blood into numerous vessels in the segments...
June 2017: Journal of Morphology
https://www.readbyqxmd.com/read/28341420/brain-metastasization-of-breast-cancer
#19
REVIEW
Tânia Custódio-Santos, Mafalda Videira, Maria Alexandra Brito
Central nervous system metastases have been reported in 15-25% of breast cancer patients, and the incidence is increasing. Moreover, the survival of these patients is generally poor, with reports of a 1-year survival rate of 20%. Therefore, a better knowledge about the determinants of brain metastasization is essential for the improvement of the clinical outcomes. Here, we summarize the current data about the metastatic cascade, ranging from the output of cancer cells from the primary tumour to their colonization in the brain, which involves the epithelial-mesenchymal transition, invasion of mammary tissue, intravasation into circulation, and homing into and extravasation towards the brain...
March 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28322181/epithelial-mesenchymal-and-hybrid-epithelial-mesenchymal-phenotypes-and-their-clinical-relevance-in-cancer-metastasis
#20
Minal Garg
Cancer metastasis occurs through local invasion of circulating tumour cells (CTCs), intravasation, transportation to distant sites, and their extravasation followed by colonisation at secondary sites. Epithelial-mesenchymal transition (EMT) is a normal developmental phenomenon, but its aberrant activation confers tumour cells with enhanced cell motility, metastatic properties, resistant to therapies and cancer stem cell (CSC) phenotype in epithelium-derived carcinoma. Experimental studies from various research papers have been reviewed to determine the factors, which interlink cancer stemness and cellular plasticity with EMT...
March 21, 2017: Expert Reviews in Molecular Medicine
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