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E-selectin metastasis

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...
October 15, 2016: 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
Yu Gao, Songen Gu, Yingying Zhang, Xiaodong Xie, Ting Yu, Yusheng Lu, Yewei Zhu, Wenge Chen, Huijuan Zhang, Haiyan Dong, Patrick J Sinko, Lee Jia
The circulating tumor cells (CTCs) existing in cancer survivors are considered the root cause of cancer metastasis. To prevent the devastating metastasis cascade from initiation, we hypothesize that a biodegradable nanomaterial loaded with the abortifacient mifepristone (MIF) and conjugated with the epithelial cell adhesion molecule antibody (aEpCAM) may serve as a safe and effective cancer metastatic preventive agent by targeting CTCs and preventing their adhesion-invasion to vascular intima. It is demonstrated that MIF-loaded mesoporous silica nanoparticles (MSN) coated with aEpCAM (aE-MSN-M) can specifically target and bind colorectal cancer cells in either cell medium or blood through EpCAM recognition proven by quantitative flow cytometric detection and free aEpCAM competitive assay...
May 2016: Small
Patrick Borentain, Sylvie Carmona, Sylvie Mathieu, Elisabeth Jouve, Assou El-Battari, René Gérolami
PURPOSE: Interactions between endothelial and tumor cells via E-selectin and sialyl Lewis x (sLex) have been suggested to play a significant role in the development of metastasis and tumor growth. In this work, we tested whether inhibition of E-selectin expression on the surface of endothelial cells might impair endothelial/tumor cells interactions and tumor growth of hepatocarcinoma cells in vitro and in vivo. METHODS: We used HepG2 cells that highly express sLex antigens and HuH7 cells that do not express sLex...
April 2016: Cancer Chemotherapy and Pharmacology
Zhou Jiang, Yaqiong Pang, Xiaobo Yu, Suxia Zhou, Jun Qian, Ning Zheng, Haiyan Dong, Qing Shi, Minliang Kuo, Lee Jia
Recent large epidemiological studies demonstrated benefit of oral contraceptives in reducing cancer risk, and our analysis also showed molecular and cellular similarities between embryo implantation and CTCs adhesion-invasion to endothelium. We here hypothesize that abortion traditional Chinese medicine (TCM) may serve well for pre-metastatic chemoprevention. To test the hypothesis, we selected the safe and well-known abortifacient TCM Murraya paniculata and identified a most-promising extracted fraction G (containing flavonoids and coumarins) from its many raw ethanol/dichloromethane extracts by using the bioactivity-guided fast screen assay...
April 19, 2016: Oncotarget
Elizabeth C Wayne, Siddarth Chandrasekaran, Michael J Mitchell, Maxine F Chan, Rachel E Lee, Chris B Schaffer, Michael R King
Prostate cancer, once it has progressed from its local to metastatic form, is a disease with poor prognosis and limited treatment options. Here we demonstrate an approach using nanoscale liposomes conjugated with E-selectin adhesion protein and Apo2L/TRAIL (TNF-related apoptosis-inducing ligand) apoptosis ligand that attach to the surface of leukocytes and rapidly clear viable cancer cells from circulating blood in the living mouse. For the first time, it is shown that such an approach can be used to prevent the spontaneous formation and growth of metastatic tumors in an orthotopic xenograft model of prostate cancer, by greatly reducing the number of circulating tumor cells...
February 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
E-M Reitter, A Kaider, C Ay, P Quehenberger, C Marosi, C Zielinski, I Pabinger
UNLABELLED: ESSENTIALS: Hemostasis biomarkers impact thrombosis occurrence and survival in cancer patients. We performed a longitudinal analysis of hemostatic parameters in 112 cancer patients. Hemostatic parameters are associated with disease state, patients' prognosis, and the risk of VTE. The procoagulant state exists not only at diagnosis, but also during the course of disease. BACKGROUND: Hemostasis biomarkers are known to have an impact on venous thromboembolism (VTE) occurrence and survival in cancer patients...
February 2016: Journal of Thrombosis and Haemostasis: JTH
Paulina Kulig, Sara Burkhard, Joanna Mikita-Geoffroy, Andrew L Croxford, Nadine Hövelmeyer, Gabor Gyülvészi, Christian Gorzelanny, Ari Waisman, Lubor Borsig, Burkhard Becher
The role of the IL23/IL17A axis in tumor-immune interactions is a matter of controversy. Although some suggest that IL17A-producing T cells (TH17) can suppress tumor growth, others report that IL17A and IL23 accelerate tumor growth. Here, we systematically assessed the impact of IL17A-secreting lymphocytes in several murine models of tumor lung metastasis. Genetic fate mapping revealed that IL17A was secreted within lung metastases predominantly by γδ T cells, whereas TH17 cells were virtually absent. Using different tumor models, we found Il17a(-/-) mice to consistently develop fewer pulmonary tumor colonies...
January 2016: Cancer Immunology Research
Arti Yadav, Bhavna Kumar, Jun-Ge Yu, Matthew Old, Theodoros N Teknos, Pawan Kumar
Tumor metastasis is a highly inefficient biological process as millions of tumor cells are released in circulation each day and only a few of them are able to successfully form distal metastatic nodules. This could be due to the fact that most of the epithelial origin cancer cells are anchorage-dependent and undergo rapid anoikis in harsh circulating conditions. A number of studies have shown that in addition to tumor cells, activated endothelial cells are also released into the blood circulation from the primary tumors...
2015: PloS One
Samah A Jassam, Zaynah Maherally, James R Smith, Keyoumars Ashkan, Federico Roncaroli, Helen L Fillmore, Geoffrey J Pilkington
BACKGROUND: CD15, which is overexpressed on various cancers, has been reported as a cell adhesion molecule that plays a key role in non-CNS metastasis. However, the role of CD15 in brain metastasis is largely unexplored. This study provides a better understanding of CD15/CD62E interaction, enhanced by tumor necrosis factor-α (TNF-α), and its correlation with brain metastasis in non-small cell lung cancer (NSCLC). METHODS: CD15 and E-selectin (CD62E) expression was demonstrated in both human primary and metastatic NSCLC cells using flow cytometry, immunofluorescence, and Western blotting...
May 2016: Neuro-oncology
Daniel J Shea, Denis Wirtz, Kathleen J Stebe, Konstantinos Konstantopoulos
Selectin-mediated tumor cell tethering to host cells, such as vascular endothelial cells, is a critical step in the process of cancer metastasis. We recently identified sialofucosylated mucin16 (MUC16) and podocalyxin (PODXL) as the major functional E- and L-selectin ligands expressed on the surface of metastatic pancreatic cancer cells. While the biophysics of leukocyte binding to selectins has been well studied, little is known about the mechanics of selectin-mediated adhesion pertinent to cancer metastasis...
September 22, 2015: Oncotarget
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