Tetraspanin family member CD9 inhibits Aggrus/podoplanin-induced platelet aggregation and suppresses pulmonary metastasis

Blood ◽  
2008 ◽  
Vol 112 (5) ◽  
pp. 1730-1739 ◽  
Author(s):  
Youya Nakazawa ◽  
Shigeo Sato ◽  
Mikihiko Naito ◽  
Yukinari Kato ◽  
Kazuhiko Mishima ◽  
...  

Abstract CD9 has been reported to play a role in tumor metastasis suppression. However, it is not fully understood how CD9 affects the hematogenous spread of tumor cells. To clarify a new mechanism (or mechanisms), we generated HT1080 cells that had been transfected with a CD9-expressing plasmid. Ectopic expression of CD9 in HT1080 cells actually reduced their metastatic ability. CD9 expression reduced lung retention and platelet ag-gregation activity of the transfectants. Because HT1080 cells express the metastasis-promoting, platelet aggregation-inducing factor Aggrus/podoplanin on their surface, we examined the relationship between CD9 and Aggrus. We discovered that CD9 formed a complex with Aggrus via transmembrane domains 1 and 2 (TM1 and TM2) of CD9. Investigation of the interaction revealed that each CD9 and Aggrus interacted homophilically, and that they colocalized in low-density membrane fractions. Deleting TM1 and TM2 attenuated the ability of CD9 to interact homophilically or to localize in low-density membrane fractions. The expression of CD9–wild-type (WT), but not CD9 lacking TM1 and TM2, attenuated the platelet aggregation and metastasis induced by forced expression of Aggrus in CHO cells. Therefore, CD9 may act as a metastasis suppressor, at least in part, by neutralizing Aggrus-mediated platelet aggregation.

1986 ◽  
Vol 55 (02) ◽  
pp. 173-177 ◽  
Author(s):  
K Desai ◽  
J S Owen ◽  
D T Wilson ◽  
R A Hutton

SummaryPlatelet aggregation, platelet lipid composition and plasma lipoprotein concentrations were measured each week in a group of seventeen alcoholics, without overt liver disease, for one month, following acute, total alcohol withdrawal. The platelets were initially hypoaggregable but, within 1-2 weeks of cessation of drinking, they became hyperaggregable and then gradually returned towards normal values. Hyperaggregability could not be explained by increases in either the cholesterol or the arachidonic acid content of the platelets. Plasma very-low-density lipoprotein cholesterol levels remained high throughout the study, but the initially raised levels of high-density lipoprotein (HDL) cholesterol fell by 26%. Low-density lipoprotein (LDL) cholesterol concentration rose by 10% after two weeks of withdrawal but then returned to about the starting level. The resulting changes in the plasma LDL-cholesterol: HDL-cholesterol ratio, which had increased by more than 50% after two weeks of abstinence, essentially paralleled the time course of enhanced platelet reactivity in all but four of the alcoholics. These findings suggest that alterations in plasma lipoprotein concentrations during acute alcohol withdrawal may be a contributory factor to the haemostatic disorders present in such patients.


2013 ◽  
Vol 98 (8) ◽  
pp. 3280-3287 ◽  
Author(s):  
Yasuyo Nakajima ◽  
Masanobu Yamada ◽  
Masako Akuzawa ◽  
Sumiyasu Ishii ◽  
Yasuhiro Masamura ◽  
...  

Context: Subclinical hypothyroidism (SCH) and metabolic syndrome (MetS) increase with age; however, their relationship remains unclear. Objective: Our objective was to investigate the relationship between SCH and indices of metabolic syndrome and follow up subjects for 1 year. Design: Cross-sectional and longitudinal follow-up studies of cases were collected from Takasaki Hidaka Hospital between 2003 and 2007. Participants: Overall, 11 498 participants of health checkups were analyzed. The mean age was 48 ± 9 years. Main Outcome Measures: The relationship between SCH and indices of MetS were examined. Results: Serum free T4 levels were lower in women than men in most of the age groups, and the prevalence of SCH, 6.3% in women vs 3.4% in men, increased with age, reaching 14.6% in 70-year-old women. Multivariate logistic-regression analyses revealed that waist circumference and the serum triglyceride and low-density lipoprotein-cholesterol levels were significantly higher in subjects with SCH than without among women. Reflecting these findings, the adjusted odds ratio of MetS in patients with SCH was higher than in the euthyroid subjects in women with an odds ratio of 2.7 (95% confidence interval 1.1–5.6; P = .017) but not in men. Furthermore, progression from euthyroid into SCH resulted in a significant increase in the serum triglyceride levels but not low-density lipoprotein-cholesterol in women. Conclusion: Japanese women exhibited a high prevalence of SCH associated with low free T4 levels. There was a strong association between SCH and several indices of metabolic syndrome in women. SCH may affect serum triglyceride levels and be a risk factor for metabolic syndrome.


2017 ◽  
Vol 50 (1) ◽  
pp. 36-57 ◽  
Author(s):  
Nurul Hidayah ◽  
Mariatti Mustapha ◽  
Hanafi Ismail ◽  
Mohamad Kamarol

This study determines the applicability of nanofillers (silica, boron nitride, and zinc oxide) in linear low-density polyethylene (LLDPE)/silicone rubber (SR) insulation compounds. Design of experiment is adopted to model the relationship between the properties (permittivity, loss tangent, dielectric strength, and volume resistivity) and factors (SR content, type of nanofiller, and nanofiller loading) for performance optimization. It is observed that SR content and type of nanofiller significantly influence the electrical properties of LLDPE/SR nanocomposites. Nanofiller loading, however, causes a small variation in the properties of the nanocomposites except for dielectric strength. From the optimization, it is found that the optimum formulation composition is 10 wt% of SR and 2 vol% of nanoboron nitride.


2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Qian Zhang ◽  
Jin-yan Wang ◽  
Wei Yan ◽  
Dan-dan Wang ◽  
Su-jin Yang ◽  
...  

Abstract Homo sapiens ceramide synthase 2 (CerS-2) plays an important role in inhibiting invasion and metastasis of tumor cells and has been reported as a tumor metastasis suppressor gene in diverse cancers. Thus, low level of CerS-2 protein might suggest a bad prognosis and up-regulation of CerS-2 protein might act as a promising therapeutic strategy for malignant tumors. In this review, we discussed the expression, as well as the clinical and pathological significance of CerS-2 in diverse human cancers. The pathological processes and molecular pathways regulated by CerS-2 were also summarized.


1995 ◽  
Vol 380 ◽  
Author(s):  
Alfred P. Weber ◽  
James D. Thorne ◽  
Sheldon K. Friedlander

ABSTRACTThe microstructure of an agglomerate can be characterized by the coordination number. The relationship between the fractal dimension and the coordination number of agglomerates of nanometer particles was investigated in experiments and computer simulations. The results for silver agglomerates formed by laser ablation agreed well with the simulations. The coordination number is low for low density fractals because of the large fraction of surface particles which have fewer bonds. The sensitivity of the coordination number to the fractal dimension increases with increasing fractal dimension.


Sign in / Sign up

Export Citation Format

Share Document