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E-selectin metastasis

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
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
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
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...
December 14, 2016: Glycoconjugate Journal
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
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
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
Hong-Xia Cui, Honglan Wang, Yuchun Wang, Juan Song, Hua Tian, Chunhui Xia, Yetong Shen
Changes in the carbohydrate structure on the surface of tumor cells is an important feature of cancer metastasis. The specific role of sialic acids in the glycoconjugate terminal has not yet been clearly elucidated in these processes. Previously, we reported that α2,3-sialic acid residues in breast cancer are associated with metastatic potential. The α2,3-sialyltransferase ST3Gal III, which adds α2,3-sialic acids to glycoproteins, is overexpressed in various tumors, and enzyme activity is correlated with tumor metastasis, yet its mechanistic role has not been fully evaluated...
December 2016: Oncology Reports
Aleksandra Korniluk, Joanna Kamińska, Paweł Kiszło, Halina Kemona, Violetta Dymicka-Piekarska
CONTEXT: Selectins probably participate in the interactions between platelets and other inflammatory cells in cancer invasion and metastasis formation. We assessed a potential relationship of P-, L- and E-selectin in colorectal cancer (CRC) patients in relation to tumour advancement according to TNM classification, and tumour location. MATERIALS AND METHODS: The study group was composed of 53 CRC patients and 25 healthy subjects. Plasma levels of soluble P-, L- and E-selectins were measured using the immunoenzymatic method with Quantikine kits (R&D Systems, Minneapolis, MN)...
November 9, 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
Katrin Anne Becker, Nadine Beckmann, Constantin Adams, Gabriele Hessler, Melanie Kramer, Erich Gulbins, Alexander Carpinteiro
Metastatic dissemination of cancer cells is one of the hallmarks of malignancy and accounts for approximately 90 % of human cancer deaths. Within the blood vasculature, tumor cells may aggregate with platelets to form clots, adhere to and spread onto endothelial cells, and finally extravasate to form metastatic colonies. We have previously shown that sphingolipids play a central role in the interaction of tumor cells with platelets; this interaction is a prerequisite for hematogenous tumor metastasis in at least some tumor models...
January 2017: Clinical & Experimental Metastasis
Irina Häuselmann, Marko Roblek, Darya Protsyuk, Volker Huck, Lucia Knopfova, Sandra Grässle, Alexander T Bauer, Stefan W Schneider, Lubor Borsig
Tumor cells interact with blood constituents and these interactions promote metastasis. Selectins are vascular receptors facilitating interactions of tumor cells with platelets, leukocytes, and endothelium, but the role of endothelial E-selectin remains unclear. Here we show that E-selectin is a major receptor for monocyte recruitment to tumor cell-activated endothelium. Experimental and spontaneous lung metastasis using murine tumor cells, without E-selectin ligands, were attenuated in E-selectin-deficient mice...
September 15, 2016: Cancer Research
Gino Stolfa, Nandini Mondal, Yuqi Zhu, Xinheng Yu, Alexander Buffone, Sriram Neelamegham
There is often interest in dissecting the relative contributions of the N-glycans, O-glycans and glycosphingolipids (GSLs) in regulating complex biological traits like cell signaling, adhesion, development and metastasis. To address this, we developed a CRISPR-Cas9 toolkit to selectively truncate each of these commonly expressed glycan-types. Here, O-glycan biosynthesis was truncated by knocking-out Core 1 β3Gal-T Specific Molecular Chaperone (COSMC), N-glycans by targeting the β1,2 GlcNAc-transferase (MGAT1) and GSLs by deleting UDP-glucose ceramide glucosyltransferase (UGCG)...
2016: Scientific Reports
Yosi Shamay, Moshe Elkabets, Hongyan Li, Janki Shah, Samuel Brook, Feng Wang, Keren Adler, Emily Baut, Maurizio Scaltriti, Prakrit V Jena, Eric E Gardner, John T Poirier, Charles M Rudin, José Baselga, Adriana Haimovitz-Friedman, Daniel A Heller
Disseminated tumors are poorly accessible to nanoscale drug delivery systems because of the vascular barrier, which attenuates extravasation at the tumor site. We investigated P-selectin, a molecule expressed on activated vasculature that facilitates metastasis by arresting tumor cells at the endothelium, for its potential to target metastases by arresting nanomedicines at the tumor endothelium. We found that P-selectin is expressed on cancer cells in many human tumors. To develop a targeted drug delivery platform, we used a fucosylated polysaccharide with nanomolar affinity to P-selectin...
June 29, 2016: Science Translational Medicine
Shin-Ae Kang, Celine A Blache, Sandra Bajana, Nafis Hasan, Mohamed Kamal, Yoshihiro Morita, Vineet Gupta, Bilegtsaikhan Tsolmon, K Stephen Suh, David G Gorenstein, Wajeeha Razaq, Hallgeir Rui, Takemi Tanaka
No abstract text is available yet for this article.
2016: BMC Cancer
Chien-Liang Lin, Shu-Ling Hsieh, Wan Leung, Jiiang-Huei Jeng, Guan-Cheng Huang, Chining-Ting Lee, Chih-Chung Wu
2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (THSG), a major component of Polygonum multiflorum Thunb (He-Shou-Wu), has been reported to exhibit antioxidant and anti-inflammatory effects. However, its anti-metastatic effect against colorectal cancer is still unclear. In this study, cell migration, invasion and adhesion abilities as well as metastasis-associated protein and NF-κB pathway signaling factor expression were analyzed after treating HT-29 cells with THSG. According to the results, the migration and invasiveness of HT-29 cells were reduced after treatment with 5 or 10 mM THSG (p<0...
August 2016: International Journal of Oncology
Shu-Ling Hsieh, Shuchen Hsieh, Yu-Hao Kuo, Jyh-Jye Wang, Jinn-Chyi Wang, Chih-Chung Wu
The goal of this study was to investigate the effect of the Panax notoginseng ethanol extract (PNEE) on the regulation of human colorectal cancer (CRC) metastasis. The migratory, invasive, and adhesive abilities and the expression of metastasis-associated regulatory molecules in cultured human CRC cells (HCT-116) treated with the PNEE were analyzed in this study. The migratory and invasive abilities of HCT-116 cells were reduced after PNEE treatment. The incubation of HCT-116 cells with the PNEE for 24 h decreased MMP-9 expression and increased E-cadherin expression compared with the control group...
2016: American Journal of Chinese Medicine
Shin-Ae Kang, Celine A Blache, Sandra Bajana, Nafis Hasan, Mohamed Kamal, Yoshihiro Morita, Vineet Gupta, Bilegtsaikhan Tsolmon, Stephen K Suh, David G Gorenstein, Wajeeha Razaq, Hallgeir Rui, Takemi Tanaka
BACKGROUND: Distant metastasis resulting from vascular dissemination of cancer cells is the primary cause of mortality from breast cancer. We have previously reported that E-selectin expression on the endothelial cell surface mediates shear-resistant adhesion and migration of circulating cancer cells via interaction with CD44. As a result of shedding, soluble E-selectin (sE-selectin) from the activated endothelium is present in the serum. In this study, we aimed to understand the role of sE-selectin in tumor progression and metastasis...
2016: BMC Cancer
Natalie Woodman, Sarah E Pinder, Virginia Tajadura, Xuefen Le Bourhis, Cheryl Gillett, Philippe Delannoy, Joy M Burchell, Sylvain Julien
Distant metastases account for the majority of cancer-related deaths in breast cancer. The rate and site of metastasis differ between estrogen receptor (ER)-negative and ER-positive tumours, and metastatic fate can be very diverse even within the ER-negative group. Characterisation of new pro-metastatic markers may help to identify patients with higher risk and improve their care accordingly. Selectin ligands aberrantly expressed by cancer cells promote metastasis by enabling interaction between circulating tumour cells and endothelial cells in distant organs...
July 2016: International Journal of Oncology
Florian Gebauer, Daniel Wicklein, Michael Tachezy, Tobias Grob, Doris Steinemann, Georgi Manukjan, Gudrun Göhring, Brigitte Schlegelberger, Hanna Maar, Jakob R Izbicki, Maximilian Bockhorn, Udo Schumacher
BACKGROUND: Non-small lung cancer is the leading cause of cancer-related mortality worldwide. For a deeper understanding of tumor biology, we established a pair of cell lines derived from a primary tumor and a corresponding lymph node metastasis. MATERIAL AND METHODS: The cell line BC4323 from the primary tumor (PT) and a mediastinal lymph node metastasis (LN) were derived from an adenocarcinoma (pT2, pN2, G3, UICC stage IIIa) in a 47-year-old female patient. Comparative characterization was performed by in vitro analysis...
April 2016: Anticancer Research
P Zhang, S Feng, G Liu, H Wang, A Fu, H Zhu, Q Ren, B Wang, X Xu, H Bai, C Dong
Melanoma is one of the most lethal forms of skin cancer because of its early metastatic spread. The variant form of CD44 (CD44v), a cell surface glycoprotein, is highly expressed on metastatic melanoma. The mechanisms of regulation of CD44 alternative splicing in melanoma and its pathogenic contributions are so far poorly understood. Here, we investigated the expression level of CD44 in a large set of melanocytic lesions at different stages. We found that the expression of CD44v8-10 and a splicing factor, U2AF2, is significantly increased during melanoma progression, whereas CD82/KAI1, a tetraspanin family of tumor suppressor, is reduced in metastatic melanoma...
September 22, 2016: Oncogene
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