Collectively migrating tumor cells have been recently implicated in enhanced metastasis of epithelial malignancies.In oral squamous cell carcinoma(OSCC),av integrin is a crucial mediator of multicellular clustering an...Collectively migrating tumor cells have been recently implicated in enhanced metastasis of epithelial malignancies.In oral squamous cell carcinoma(OSCC),av integrin is a crucial mediator of multicellular clustering and collective movement in vitro;however,its contribution to metastatic spread remains to be addressed.According to the emerging therapeutic concept,dissociation of tumor clusters into single cells could significantly suppress metastasis-seeding ability of carcinomas.This study aimed to investigate the anti-OSCC potential of novel endostatin-derived polypeptide PEP06 as a clusterdissociating therapeutic agent in vitro.Firstly,we found marked enrichment ofαv integrin in collectivelyinvading multicellular clusters in human OSCCs.Our study revealed that metastatic progression of OSCC was associated with augmented immunostaining of av integrin in cancerous lesions.Following PEP06treatment,cell clustering on fibronectin,migration,multicellular aggregation,anchorage-independent survival and colony formation of OSCC were significantly inhibited.Moreover,PEP06 suppressed av integrin/FAK/Sre signaling in OSCC cells.PEP06-induced loss of active Src and E-cadherin from cell-cell contacts contributed to diminished collective migration of OSCC in vitro.Overall,these results suggest that PEP06 polypeptide 30 inhibiting av integrin/FAK/Src signaling and disrupting E-cadherin-based intercellular junctions possesses anti-metastatic potential in OSCC by acting as a cluster-dissociating therapeutic agent.展开更多
Objective： To investigate whether the cell adhesion molecule integrin αV could influence the radiosensitivity of human nasopharyngeal carcinoma CNE-2Z cells via effecting intercellular effect. Methods： Human NPC ce...Objective： To investigate whether the cell adhesion molecule integrin αV could influence the radiosensitivity of human nasopharyngeal carcinoma CNE-2Z cells via effecting intercellular effect. Methods： Human NPC cell line CNE-2Z was cultivated as three dimensional model using liquid overlay technique. Cell counting was employed to detect the radiosensitivity of CNE-2Z cells by blood cell counter before and after blocking integrin aV function; cell apoptosis was detected by flow cytometry using Annexin V/PI label. Results： Three dimensional culture model of human NPC cell line CNE-2Z cells were successfully established. The integrin αV expression of CNE-2Z multicellular spheroids elevated as the dosage of radiotherapy increased. Blocking of integrin aV function leaded to higher radiosensitivity and more apoptotic cells of CNE-2Z multicellular spheroids. Conclusion： Cell adhesion molecules integrin aV can influence the radiosensitivity of human nasopharyngeal carcinoma CNE-2Z cells and the inhibition of cell apoptosis might be its mechanism, proved by three dimensional culture model to mimic solid tumor in vivo.展开更多
Buyanghuanwu decoction has been shown to protect against cerebral ischemia/reperfusion injury,but the underlying mechanisms remain unclear.In this study,rats were intragastrically given Buyanghuanwu decoction,15 m L/k...Buyanghuanwu decoction has been shown to protect against cerebral ischemia/reperfusion injury,but the underlying mechanisms remain unclear.In this study,rats were intragastrically given Buyanghuanwu decoction,15 m L/kg,for 3 days.A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion.In rats administered Buyanghuanwu decoction,infarct volume was reduced,serum vascular endothelial growth factor and integrin αvβ3 levels were increased,and brain tissue vascular endothelial growth factor and CD34 expression levels were increased compared with untreated animals.These effects of Buyanghuanwu decoction were partially suppressed by an angiogenesis inhibitor（administered through the lateral ventricle for 7 consecutive days）.These data suggest that Buyanghuanwu decoction promotes angiogenesis,improves cerebral circulation,and enhances brain tissue repair after cerebral ischemia/reperfusion injury.展开更多
基金funded by the National Natural Science Foundation of China(grant Nos.81730012 and 81673426)the Grant of Republic Bashkortostan for Young Scientists(grant No.26 GR).
文摘Collectively migrating tumor cells have been recently implicated in enhanced metastasis of epithelial malignancies.In oral squamous cell carcinoma(OSCC),av integrin is a crucial mediator of multicellular clustering and collective movement in vitro;however,its contribution to metastatic spread remains to be addressed.According to the emerging therapeutic concept,dissociation of tumor clusters into single cells could significantly suppress metastasis-seeding ability of carcinomas.This study aimed to investigate the anti-OSCC potential of novel endostatin-derived polypeptide PEP06 as a clusterdissociating therapeutic agent in vitro.Firstly,we found marked enrichment ofαv integrin in collectivelyinvading multicellular clusters in human OSCCs.Our study revealed that metastatic progression of OSCC was associated with augmented immunostaining of av integrin in cancerous lesions.Following PEP06treatment,cell clustering on fibronectin,migration,multicellular aggregation,anchorage-independent survival and colony formation of OSCC were significantly inhibited.Moreover,PEP06 suppressed av integrin/FAK/Sre signaling in OSCC cells.PEP06-induced loss of active Src and E-cadherin from cell-cell contacts contributed to diminished collective migration of OSCC in vitro.Overall,these results suggest that PEP06 polypeptide 30 inhibiting av integrin/FAK/Src signaling and disrupting E-cadherin-based intercellular junctions possesses anti-metastatic potential in OSCC by acting as a cluster-dissociating therapeutic agent.
文摘Objective： To investigate whether the cell adhesion molecule integrin αV could influence the radiosensitivity of human nasopharyngeal carcinoma CNE-2Z cells via effecting intercellular effect. Methods： Human NPC cell line CNE-2Z was cultivated as three dimensional model using liquid overlay technique. Cell counting was employed to detect the radiosensitivity of CNE-2Z cells by blood cell counter before and after blocking integrin aV function; cell apoptosis was detected by flow cytometry using Annexin V/PI label. Results： Three dimensional culture model of human NPC cell line CNE-2Z cells were successfully established. The integrin αV expression of CNE-2Z multicellular spheroids elevated as the dosage of radiotherapy increased. Blocking of integrin aV function leaded to higher radiosensitivity and more apoptotic cells of CNE-2Z multicellular spheroids. Conclusion： Cell adhesion molecules integrin aV can influence the radiosensitivity of human nasopharyngeal carcinoma CNE-2Z cells and the inhibition of cell apoptosis might be its mechanism, proved by three dimensional culture model to mimic solid tumor in vivo.
基金financially supported by the National Natural Science Foundation of China,No.81072799
文摘Buyanghuanwu decoction has been shown to protect against cerebral ischemia/reperfusion injury,but the underlying mechanisms remain unclear.In this study,rats were intragastrically given Buyanghuanwu decoction,15 m L/kg,for 3 days.A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion.In rats administered Buyanghuanwu decoction,infarct volume was reduced,serum vascular endothelial growth factor and integrin αvβ3 levels were increased,and brain tissue vascular endothelial growth factor and CD34 expression levels were increased compared with untreated animals.These effects of Buyanghuanwu decoction were partially suppressed by an angiogenesis inhibitor（administered through the lateral ventricle for 7 consecutive days）.These data suggest that Buyanghuanwu decoction promotes angiogenesis,improves cerebral circulation,and enhances brain tissue repair after cerebral ischemia/reperfusion injury.
