{"title":"Akt pathway activation reduces platelet apoptosis and contributes to the increase of platelet counts in solid tumor patients.","authors":"Huan Tian, Songyin Huang, Qing Luo, Zhuochen Lin, Huanhuan Liu, Zhixian Zhang, Wengcheng Fong, Jinghua Zhao, Fengyan Yu","doi":"10.1080/09537104.2022.2026908","DOIUrl":null,"url":null,"abstract":"<p><p>Platelets counts increase in various cancer patients, which is associated with poor prognosis. However, the cause of high platelet counts in cancer patients is still not fully understood. Here we demonstrated that compared with healthy controls, there were significant differences in platelet parameters, mean platelet volume (MPV), platelet distribution width (PDW), platelet larger cell ratio (P-LCR), and platelet crit (PCT), reflecting platelet volume in breast cancer patients by clinical retrospective analysis. The mitochondrial transmembrane potential (ΔΨm) depolarization and phosphatidylserine (PS) externalization declined, accompanied by reduced expression of pro-apoptotic factors Bak, Bax and apoptotic executor caspase-3, and elevated of anti-apoptotic factor Bcl-xl in various cancer patients' platelets. Notably, the phosphorylation level of Akt and its downstream target Bad increased in platelets from cancer patients. MK2206, the inhibitor of Akt, reduced the phosphorylation level of Akt and Bad, and induced apoptosis of platelets. When platelets from healthy controls cocultured with the cultural supernatant of cancer cells, the phosphorylation level of Akt and Bad in the platelets was elevated and the cultural supernatant of cancer cells could rescue the apoptosis of platelet induced by MK2206. Therefore, in our study the apoptosis of platelets in cancer patients was declined, which exerted an influence on the rise of platelet counts in breast cancer patients. The cross-talking between tumor and platelets could affect platelet apoptosis by regulating Akt signaling pathway in platelets.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"1009-1017"},"PeriodicalIF":4.6000,"publicationDate":"2022-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"3","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/09537104.2022.2026908","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/1/24 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 3
Abstract
Platelets counts increase in various cancer patients, which is associated with poor prognosis. However, the cause of high platelet counts in cancer patients is still not fully understood. Here we demonstrated that compared with healthy controls, there were significant differences in platelet parameters, mean platelet volume (MPV), platelet distribution width (PDW), platelet larger cell ratio (P-LCR), and platelet crit (PCT), reflecting platelet volume in breast cancer patients by clinical retrospective analysis. The mitochondrial transmembrane potential (ΔΨm) depolarization and phosphatidylserine (PS) externalization declined, accompanied by reduced expression of pro-apoptotic factors Bak, Bax and apoptotic executor caspase-3, and elevated of anti-apoptotic factor Bcl-xl in various cancer patients' platelets. Notably, the phosphorylation level of Akt and its downstream target Bad increased in platelets from cancer patients. MK2206, the inhibitor of Akt, reduced the phosphorylation level of Akt and Bad, and induced apoptosis of platelets. When platelets from healthy controls cocultured with the cultural supernatant of cancer cells, the phosphorylation level of Akt and Bad in the platelets was elevated and the cultural supernatant of cancer cells could rescue the apoptosis of platelet induced by MK2206. Therefore, in our study the apoptosis of platelets in cancer patients was declined, which exerted an influence on the rise of platelet counts in breast cancer patients. The cross-talking between tumor and platelets could affect platelet apoptosis by regulating Akt signaling pathway in platelets.
期刊介绍:
ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications.
The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.