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E-selectin metastasis

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https://www.readbyqxmd.com/read/29215790/inhibition-of-fucosylation-in-human-invasive-ductal-carcinoma-reduces-e-selectin-ligand-expression-cell-proliferation-and-erk1-2-and-p38-mapk-activation
#1
M A Carrascal, M Silva, J S Ramalho, C Pen, M Martins, C Pascoal, C Amaral, I Serrano, M J Oliveira, R Sackstein, P A Videira
Breast cancer tissue overexpresses fucosylated glycans, such as sialyl-Lewis X/A (sLeX/A ), and α-1,3/4-fucosyltransferases in relation to increased disease progression and metastasis. These glycans in tumor circulating cells mediate binding to vascular E-selectin, initiating tumor extravasation. However, their role(s) in breast carcinogenesis is still unknown. Here, we aimed to define the contribution of the fucosylated structures, including sLeX/A , to cell adhesion, cell signaling and proliferation in invasive ductal carcinomas (IDC), the most frequent type of breast cancer...
December 7, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29188480/a-function-blocking-cd47-antibody-modulates-extracellular-vesicle-mediated-intercellular-signaling-between-breast-carcinoma-cells-and-endothelial-cells
#2
Sukhbir Kaur, Abdel G Elkahloun, Satya P Singh, Anush Arakelyan, David D Roberts
Tumor cells release extracellular vesicles (EVs) into the tumor microenvironment that may facilitate malignant progression and metastasis. Breast carcinoma EVs express high levels of the thrombospondin-1 and signal regulatory protein-α receptor CD47, which is the target of several experimental therapeutics currently in clinical trials. We analyzed changes in gene expression and function in human umbilical vein endothelial cells (HUVEC) induced by treatment with EVs derived from breast carcinoma cells and the effects of the function-blocking CD47 antibody B6H12 on the resulting intercellular communication...
November 29, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29164060/tissue-factor-expressing-tumor-derived-extracellular-vesicles-activate-quiescent-endothelial-cells-via-protease-activated-receptor-1
#3
Sara P Y Che, Jeannie Y Park, Tracy Stokol
Tissue factor (TF)-expressing tumor-derived extracellular vesicles (EVs) can promote metastasis and pre-metastatic niche formation, but the mechanisms by which this occurs remain largely unknown. We hypothesized that generation of activated factor X (FXa) by TF expressed on tumor-derived EV could activate protease-activated receptors (PARs) on non-activated endothelial cells to induce a pro-adhesive and pro-inflammatory phenotype. We obtained EV from TF-expressing breast (MDA-MB-231) and pancreatic (BxPC3 and Capan-1) tumor cell lines...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29162703/deformability-of-breast-cancer-cells-in-correlation-with-surface-markers-and-cell-rolling
#4
Amina Mohammadalipour, Monica M Burdick, David F J Tees
Although the cancer stem cell (CSC) hypothesis has been around for many years, the reliability of cell-surface markers to classify CSCs has remained debatable. The finding that cancerous cells are significantly more deformable than healthy ones has provided motivation to consider mechanical properties as a possible biomarker for stemness. In this study, using the micropipette aspiration technique, mechanical properties of multiple breast cancer cell lines were investigated and correlated with breast cancer stem cell (BCSC) marker, CD44(+)/CD24(-)/ALDH1(+) The results indicated that Hs578T and MDA-MB-231 cell lines with CD44(+)/CD24(-)/ALDH1(+) phenotype were significantly more deformable than the MDA-MB-468 cell line, which did not express the BCSC marker...
November 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29080832/sda-and-ida-two-aptamers-to-inhibit-cancer-cell-adhesion
#5
Ulrich Hahn
Aptamers which bind to proteins involved in cell-cell interactions could have significant value to directly affect cancer adhesion or for directed cargo delivery. Here, we discuss two aptamers: aptamer SDA which binds to E- and P-selectin, and aptamer IDA which binds to α6β4 integrin. Both aptamers (SDA 91 nt and IDA 77 nt) bind their target proteins with dissociation constants in the 100-150 nM range and substantially inhibit special cellular adhesion, possibly a first and pivotal step in transendothelial migration during metastasis formation...
October 25, 2017: Biochimie
https://www.readbyqxmd.com/read/28860805/fucosyltransferase-vii-promotes-proliferation-via-the-egfr-akt-mtor-pathway-in-a549-cells
#6
Jin-Xiao Liang, Wei Gao, Lei Cai
Fucosyltransferase VII (FUT7) is one of a1,3-fucosyltransferases family that catalyzes the final fucosylation step in the synthesis of Lewis antigens and generates a unique glycosylated product sialyl Lewis X (sLe(X)). sLe(X) can serve as ligands for E- or P-selectin expressed on the cell surface and results in cancer metastasis and angiogenesis. However, the molecular biological mechanisms of FUT7 elevation in neoplastic cells are still largely unknown. In this study, we examined the impact of FUT7 on cell proliferation and migration in A549 cells by colony formation assay, cell cycle assay, gelatin zymography, wound-healing assay, transwell invasion assay and Western blot...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28842850/a-flavonoid-glycoside-compound-from-murraya-paniculata-l-interrupts-metastatic-characteristics-of-a549-cells-by-regulating-stat3-nf-%C3%AE%C2%BAb-cox-2-and-egfr-signaling-pathways
#7
Qing Shi, Zhou Jiang, Jingyi Yang, Yunlong Cheng, Yaqiong Pang, Ning Zheng, Jiahang Chen, Wenge Chen, Lee Jia
Metastasis remains the leading cause of death from lung carcinoma. It is urgent to find safe and efficient pre-metastasis preventive agents for cancer survivors. We isolated a flavonoid glycoside, hexamethoxy flavanone-o-[rhamnopyranosyl-(1 → 4)-rhamnopyranoside (HMFRR), from the traditional Chinese medicine (TCM) Murraya paniculata (L.) that can effectively inhibit the adhesion, migration, and invasion of lung adenocarcinoma A549 cells in vitro. Molecular and cellular studies demonstrated that HMFRR significantly downregulated the expressions of cell adhesion-related and invasion-related molecules such as integrin β1, EGFR, COX-2, MMP-2, and MMP-9 proteins...
November 2017: AAPS Journal
https://www.readbyqxmd.com/read/28765175/e-selectin-mediated-rolling-facilitates-pancreatic-cancer-cell-adhesion-to-hyaluronic-acid
#8
Daniel J Shea, Yi W Li, Kathleen J Stebe, Konstantinos Konstantopoulos
Tumor cell extravasation is a multistep process preceded by cell rolling and arrest on the vessel wall via the formation of specific receptor-ligand bonds. The strength, availability, and number of receptor-ligand bonds regulate the rate by which tumor cells tether, roll, and adhere to vascular walls. Although the mechanics of selectin-mediated rolling have been extensively studied, little is known regarding how tumor cell rolling on selectins facilitates adhesion to a distinct substrate-bound protein with different kinetic properties...
August 1, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28698503/cd15s-cd62e-interaction-mediates-the-adhesion-of-non-small-cell-lung-cancer-cells-on-brain-endothelial-cells-implications-for-cerebral-metastasis
#9
Samah A Jassam, Zaynah Maherally, James R Smith, Keyoumars Ashkan, Federico Roncaroli, Helen L Fillmore, Geoffrey J Pilkington
Expression of the cell adhesion molecule (CAM), Sialyl Lewis X (CD15s) correlates with cancer metastasis, while expression of E-selectin (CD62E) is stimulated by TNF-α. CD15s/CD62E interaction plays a key role in the homing process of circulating leukocytes. We investigated the heterophilic interaction of CD15s and CD62E in brain metastasis-related cancer cell adhesion. CD15s and CD62E were characterised in human brain endothelium (hCMEC/D3), primary non-small cell lung cancer (NSCLC) (COR-L105 and A549) and metastatic NSCLC (SEBTA-001 and NCI-H1299) using immunocytochemistry, Western blotting, flow cytometry and immunohistochemistry in human brain tissue sections...
July 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28585149/inhibition-of-adhesion-and-metastasis-of-hepg2-hepatocellular-carcinoma-cells-in-vitro-by-dna-aptamer-against-sialyl-lewis-x
#10
Xiao-Kang Wang, Yan Peng, Hao-Ran Tao, Fen-Fang Zhou, Chi Zhang, Fei Su, Shi-Pei Wang, Qing Liu, Li-Hua Xu, Xue-Kai Pan, Wei Xie, Mao-Hui Feng
The sialyl Lewis X (SLe(x)) antigen encoded by the FUT7 gene is the ligand of endotheliam-selectin (E-selectin). The combination of SLe(x) antigen and E-selectin represents an important way for malignant tumor metastasis. In the present study, the effect of the SLe(x)-binding DNA aptamer on the adhesion and metastasis of hepatocellular carcinoma HepG2 cells in vitro was investigated. Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence staining were conducted to detect the expression of FUT7 at both transcriptional and translational levels...
June 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28576551/free-paclitaxel-loaded-e-selectin-binding-peptide-modified-micelle-self-assembled-from-hyaluronic-acid-paclitaxel-conjugate-inhibit-breast-cancer-metastasis-in-a-murine-model
#11
Xiaofeng Han, Xuerong Dong, Jing Li, Manyuan Wang, Lei Luo, Zhaoxia Li, Xuran Lu, Rui He, Rongsong Xu, Muxin Gong
The present work seeks to construct a nanovehicle for the efficient suppression of breast cancer metastasis through targeting E-selectin on tumor vascular endothelial cells and hyaluronic acid-receptor on tumor cells. Herein, a new ligand-PEG-lipid conjugate, E-selectin binding peptide-polyethene glycol-1-octadecylamine (Esbp-PEG-OA), was used as the targeting molecule of micelle self-assembled form hyaluronic acid-paclitaxel (HA-PTX) conjugate. When loaded with free PTX, the micelles (Esbp-HA-PTX/PTX) exhibited nanoscale particle size with high drug-loading capacity (up to 31...
August 7, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28534515/stat3-activation-in-endothelial-cells-is-important-for-tumor-metastasis-via-increased-cell-adhesion-molecule-expression
#12
K-J Kim, S-H Kwon, J-H Yun, H-S Jeong, H-R Kim, E H Lee, S-K Ye, C-H Cho
Metastasis is a life-threatening feature of cancer and is primarily responsible for cancer patient mortality. Cross talk between tumor cells and endothelium is important for tumor progression and metastasis. However, very little is known about the mechanisms by which endothelial cells (ECs) that are close to tumor cells, respond to the tumor cells during tumor progression and metastasis. In this study, we exploited the use of EC-specific signal transducer activator of transcription 3 (STAT3) knockout mice to investigate the role of STAT3 in ECs in tumor progression and metastasis...
September 28, 2017: Oncogene
https://www.readbyqxmd.com/read/28507122/control-of-metastatic-niche-formation-by-targeting-apba3-mint3-in-inflammatory-monocytes
#13
Toshiro Hara, Hiroki J Nakaoka, Tetsuro Hayashi, Kouhei Mimura, Daisuke Hoshino, Masahiro Inoue, Fumitaka Nagamura, Yoshinori Murakami, Motoharu Seiki, Takeharu Sakamoto
Cancer metastasis is intricately orchestrated by both cancer and normal cells, such as endothelial cells and macrophages. Monocytes/macrophages, which are often co-opted by cancer cells and promote tumor malignancy, acquire more than half of their energy from glycolysis even during normoxic conditions. This glycolytic activity is maintained during normoxia by the functions of hypoxia inducible factor 1 (HIF-1) and its activator APBA3. The mechanism by which APBA3 inhibition partially suppresses macrophage function and affects cancer metastasis is of interest in view of avoidance of the adverse effects of complete suppression of macrophage function during therapy...
May 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28439107/e-selectin-ligands-recognised-by-heca452-induce-drug-resistance-in-myeloma-which-is-overcome-by-the-e-selectin-antagonist-gmi-1271
#14
A Natoni, T A G Smith, N Keane, C McEllistrim, C Connolly, A Jha, M Andrulis, E Ellert, M S Raab, S V Glavey, L Kirkham-McCarthy, S K Kumar, S C Locatelli-Hoops, I Oliva, W E Fogler, J L Magnani, M E O'Dwyer
Multiple Myeloma (MM) is characterized by the clonal expansion and metastatic spread of malignant plasma cells to multiple sites in the bone marrow (BM). Recently, we implicated the sialyltransferase ST3Gal-6, an enzyme critical to the generation of E-selectin ligands, in MM BM homing and resistance to therapy. Since E-selectin is constitutively expressed in the BM microvasculature, we wished to establish the contribution of E-selectin ligands to MM biology. We report that functional E-selectin ligands are restricted to a minor subpopulation of MM cell lines which, upon expansion, demonstrate specific and robust interaction with recombinant E-selectin in vitro...
April 25, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28282455/dynamic-biochemical-tissue-analysis-detects-functional-l-selectin-ligands-on-colon-cancer-tissues
#15
Grady E Carlson, Eric W Martin, Venktesh S Shirure, Ramiro Malgor, Vicente A Resto, Douglas J Goetz, Monica M Burdick
A growing body of evidence suggests that L-selectin ligands presented on circulating tumor cells facilitate metastasis by binding L-selectin presented on leukocytes. Commonly used methods for detecting L-selectin ligands on tissues, e.g., immunostaining, are performed under static, no-flow conditions. However, such analysis does not assay for functional L-selectin ligands, specifically those ligands that promote adhesion under shear flow conditions. Recently our lab developed a method, termed dynamic biochemical tissue analysis (DBTA), to detect functional selectin ligands in situ by probing tissues with L-selectin-coated microspheres under hemodynamic flow conditions...
2017: PloS One
https://www.readbyqxmd.com/read/28093478/long-noncoding-rna-malat1-regulates-cerebrovascular-pathologies-in-ischemic-stroke
#16
Xuejing Zhang, Xuelian Tang, Kai Liu, Milton H Hamblin, Ke-Jie Yin
The study was designed to determine the role of long noncoding RNA (lncRNA), metastasis-associated lung adenocarcinoma transcript 1 (Malat1), in ischemic stroke outcome. Primary mouse brain microvascular endothelial cells (BMECs) were cultured and treated with Malat1 GapmeR before 16 h oxygen and glucose depravation (OGD). Cell death was assayed by LDH and MTT methods. Malat1 knock-out and wild-type mice were subjected to 1 h of middle cerebral artery occlusion (MCAO) and 24-72 h of reperfusion. To explore the underlying mechanism, apoptotic and inflammatory factors were measured by qPCR, ELISA, and Western blotting...
February 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27975160/glycosylation-a-hallmark-of-cancer
#17
REVIEW
Bhairavi N Vajaria, Prabhudas S Patel
The hallmarks of cancer are characterized by functional capabilities that allow cancer cells to survive, proliferate and disseminate during the multistep tumorigenesis. Cancer being a cellular disease, changes in cellular glycoproteins play an important role in malignant transformation and cancer progression. The present review summarizes various studies that depicted correlation of glycosylation with tumor initiation, progression and metastasis, which are helpful in early diagnosis, disease monitoring and prognosis...
April 2017: Glycoconjugate Journal
https://www.readbyqxmd.com/read/27959340/e-selectin-targeting-pegylated-thioaptamer-prevents-breast-cancer-metastases
#18
Yoshihiro Morita, Mohamed Kamal, Shin-Ae Kang, Roy Zhang, Ganesh Lr Lokesh, Varatharasa Thiviyanathan, Nafis Hasan, Sukyung Woo, Daniel Zhao, Macall Leslie, Stephen Suh, Wajeeha Razaq, Hallgeir Rui, David G Gorenstein, David E Volk, Takemi Tanaka
E-selectin is an adhesion molecule expressed on the luminal surface of inflamed blood vessels that mediates hematogenous metastasis by assisting shear-resistant adhesion of circulating tumor cells to the vessel surface under dynamic blood flow. Previously, we developed an E-selectin antagonistic thioaptamer (ESTA) for the prevention of hematogenous metastasis through the blockade of CD44(high) breast cancer cells (BCa) adhesion to E-selectin-expressing premetastatic endothelial niche. The current study focuses on developing a PEGylated E-selectin targeting thioaptamer with improved pharmaceutical properties...
December 13, 2016: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/27956273/high-endothelial-venule-like-vessels-and-lymphocyte-recruitment-in-diffuse-sclerosing-variant-of-papillary-thyroid-carcinoma
#19
Shulin Low, Yasuhiro Sakai, Hitomi Hoshino, Mitsuyoshi Hirokawa, Hiroto Kawashima, Kayoko Higuchi, Yoshiaki Imamura, Motohiro Kobayashi
Diffuse sclerosing variant of papillary thyroid carcinoma (DSPTC) is a rare subtype of papillary thyroid carcinoma with a high incidence of lymph node metastasis. One of its characteristic histological features is the presence of dense lymphocyte infiltrates; however, how these lymphocytes are recruited in this pathological setting remains unclear. Here, we analysed 17 DSPTC cases immunohistologically for cell adhesion molecules expressed on endothelial cells. We found that venules morphologically similar to high endothelial venules (HEVs) in secondary lymphoid organs were induced in lymphoid aggregates in DSPTC, and such HEV-like vessels expressed 6-sulfo sialyl Lewis X (sLeX) glycans as well as intercellular adhesion molecule 1 (ICAM-1)...
December 2016: Pathology
https://www.readbyqxmd.com/read/27885671/recruited-monocytic-myeloid-derived-suppressor-cells-promote-the-arrest-of-tumor-cells-in-the-premetastatic-niche-through-an-il-1%C3%AE-mediated-increase-in-e-selectin-expression
#20
Huifang Shi, Juechao Zhang, Xiaoqing Han, Huihan Li, Mingshu Xie, Yingying Sun, Wenguang Liu, Xueqing Ba, Xianlu Zeng
The tumor premetastatic niche initiated by primary tumors is constructed by multiple molecular factors and cellular components and provides permissive condition that allows circulating tumor cells to successfully metastasize. Myeloid-derived suppressor cells (MDSCs), a population of immature cells in pathological conditions, play a critical role in the formation of the premetastatic niche. However, few researches are focused on the function of monocytic MDSCs (mo-MDSCs), a subtype of MDSCs, in the construction of the niche...
March 15, 2017: International Journal of Cancer. Journal International du Cancer
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