Extracellular vesicles (EVs) play important roles in intercellular communication in various biological events. In particular, EVs released from cancer cells have attracted special attention. Although it has been reported that cancer-associated glycosphingolipids play important roles in the enhancement of malignant properties of cancer cells, the presence, behavior, and roles of glycosphingolipids in EVs have not been elucidated. Recently, we reported crucial roles of EVs expressing gangliosides, GD2, and/or GD3 in the enhancement of cancer properties in malignant melanomas and gliomas. However, how EVs containing cancer-associated glycosphingolipids play their roles has not been reported to date. Here, we studied spatio-temporal mechanisms for GD3/GD2-containing EVs released from gliomas in the actions toward target cells. Proteome analyses of EVs with/without GD3/GD2 revealed an equally high concentration of integrin isoforms in both GD3/GD2+ and GD3/GD2- EVs. PKH26-labeled EVs attached, invaded, and distributed to/in the target cells within 1 h. GD3/GD2 formed molecular complexes with integrins on EVs as elucidated by immunoprecipitation/immunoblotting and immunocytostaining. The addition of antibodies reactive with GD3, GD2, or integrins resulted in the suppression of the enhancing effects of EVs in the cell adhesion assay. The addition of GD3/GD2 + EVs to GD3/GD2- cells clearly increased the phosphorylation levels of the PDGF receptor, FAK, and Erk1/2 in immunoblotting, suggesting GD3/GD2+ EVs activate the signaling pathway in the target cells within 15 min after addition. Anti-ganglioside antibodies clearly blocked signaling with EVs. In conclusion, EVs released from GD3/GD2-expressing glioma cells enhance cancer phenotypes and malignant signals via the cluster formation of integrins and GD3/GD2 on EVs, leading to the regulation of the cancer microenvironment.

Background: Betel quid (BQ) chewing is a common habit and a means of social interaction among the northeastern peoples of Bangladesh. Though this habit integrating in their daily life without knowing its toxic effect. Areca nut, which is one of the main components of BQ and may responsible for this addiction. Here, we assess to see how BQ chewing habit influence hyperglycemia among diabetic patients with respect to their lifestyle. Methodology: Random blood sugar (RBS) test was evaluated from a total of 961 diabetic patients. Behavioral data associated with their daily lifestyle were collected from August 2018 to February 2019 from Sylhet Diabetic Hospital, Bangladesh. Student’s t-test, ANOVA and Fisher’s exact test were used to assess the RBS status between BQ chewer and non-chewer patients. Results: Higher RBS was found in BQ chewer patients than non-chewer (mean ± SEM, 263.3 ± 4.768 vs. 251.0 ± 5.915mg/dl). Interestingly, it is significantly higher in raw areca nut user than dry nut (mean ± SEM, 278.0 ± 8.790 vs. 252.1 ± 6.835 mg/dl) only from BQ chewer group, suggesting that the habit of chewing raw nut may contribute to more hyperglycemic effect among diabetic patients. BQ habit enhances higher RBS level among smoker, non-smoker and patient’s having walking habit. In addition, BQ habit significantly influence to have high RBS in patients with family history with diabetes. Lack of awareness being diabetes have also been observed significantly in BQ chewer patients, while a higher level of RBS was seen in BQ group, who work in different sectors with sitting activities. Conclusions: Diabetic patients who chew betel quid are more prone to keep higher hyperglycemic. Utmost attention should be taken to discourage the use of BQ for proper management of diabetes control.