Integrins mediate cell adhesion and transmit cellular chemical and mechanical signals bidirectionally.Abnormal activation of integrin signals drives tumor initiation,invasion,metastasis,and therapeutic resistance.Ther...Integrins mediate cell adhesion and transmit cellular chemical and mechanical signals bidirectionally.Abnormal activation of integrin signals drives tumor initiation,invasion,metastasis,and therapeutic resistance.Therefore,integrins are ideal tumor theranostic biomarkers.Among the 24 known human integrins,the integrinαvβ3 has been the most intensively studied in tumor theranostics in the past 20 years.Here,we focus on the laminin receptors integrinα6β1 andα6β4,which consist of theα6 integrin subunit and either theβ1 orβ4 integrin subunit,respectively.Both of these proteins are overexpressed in many cancers,and their expression has been linked to poor prognosis in some cancers.Over the last decade,we and our collaborators have developed several types of integrinα6-targeted probes,including single-photon emission computed tomography(SPECT),positron emission tomography(PET),magnetic resonance imaging(MRI)and near-infrared fluorescent imaging(NIRF)probes,for the molecular imaging of tumors.Among them,an integrinα6-targeted SPECT probe has been proven to be safe and efficient for detecting breast cancer in the first-in-human pilot study.Moreover,we have developed integrinα6-targeted therapeutic strategies for the treatment of tumors.In this review,we highlight the latest progress in integrinα6-targeted tumor theranostics.展开更多
The angiogenic response is essential for the repair of ischemic brain tissue.Integrin α6(Itga6)expression has been shown to increase under hypoxic conditions and is expressed exclusively in vascular structures;howeve...The angiogenic response is essential for the repair of ischemic brain tissue.Integrin α6(Itga6)expression has been shown to increase under hypoxic conditions and is expressed exclusively in vascular structures;however,its role in post-ischemic angiogenesis remains poorly understood.In this study,we demonstrate that mice with endothelial cell-specific knockout of Itga6 exhibit reduced neovascularization,reduced pericyte coverage on microvessels,and accelerated breakdown of microvascular integrity in the peri-infarct area.In vitro,endothelial cells with ITGA6 knockdown display reduced proliferation,migration,and tube-formation.Mechanistically,we demonstrated that ITGA6 regulates post-stroke angiogenesis through the PI3K/Akt-eNOS-VEGFA axis.Importantly,the specific overexpression of Itga6 in endothelial cells significantly enhanced neovascularization and enhanced the integrity of microvessels,leading to improved functional recovery.Our results suggest that endothelial cell Itga6 plays a crucial role in key steps of post-stroke angiogenesis,and may represent a promising therapeutic target for promoting recovery after stroke.展开更多
目的:分析二肽基肽酶样蛋白-6(dipeptidyl-peptidase-like protein 6,DPPX)抗体相关脑炎患者的临床特征。方法:对2016年1月—2025年2月南京医科大学附属脑科医院就诊的5例DPPX抗体相关脑炎患者的临床特点、脑电图、磁共振成像(magnetic ...目的:分析二肽基肽酶样蛋白-6(dipeptidyl-peptidase-like protein 6,DPPX)抗体相关脑炎患者的临床特征。方法:对2016年1月—2025年2月南京医科大学附属脑科医院就诊的5例DPPX抗体相关脑炎患者的临床特点、脑电图、磁共振成像(magnetic resonance imaging,MRI)及预后进行回顾性研究。结果:5例均为男性,年龄14~56岁。5例患者血清DPPX抗体均为阳性,滴度1∶100~1∶10,其中1例合并血清接触蛋白关联蛋白2(contactin-associated protein-like 2,CASPR2)抗体阳性,4例脑脊液DPPX抗体阴性,1例滴度1∶1。2例患者以行为异常起病,1例以癫痫发作起病,1例以记忆力减退起病,1例合并CASPR2抗体阳性患者以多部位游走性肌阵挛起病。4例患者头颅MRI正常,1例头颅MRI提示双侧颞叶异常信号。以癫痫发作起病的患者脑电图背景重度异常合并左前颞尖波、尖慢波频发。结论:DPPX抗体相关脑炎临床表现具有异质性,早期诊断与鉴别困难,免疫治疗有效,易复发。展开更多
基金supported by grants from the National Natural Science Foundation of China(82373175,82373174).
文摘Integrins mediate cell adhesion and transmit cellular chemical and mechanical signals bidirectionally.Abnormal activation of integrin signals drives tumor initiation,invasion,metastasis,and therapeutic resistance.Therefore,integrins are ideal tumor theranostic biomarkers.Among the 24 known human integrins,the integrinαvβ3 has been the most intensively studied in tumor theranostics in the past 20 years.Here,we focus on the laminin receptors integrinα6β1 andα6β4,which consist of theα6 integrin subunit and either theβ1 orβ4 integrin subunit,respectively.Both of these proteins are overexpressed in many cancers,and their expression has been linked to poor prognosis in some cancers.Over the last decade,we and our collaborators have developed several types of integrinα6-targeted probes,including single-photon emission computed tomography(SPECT),positron emission tomography(PET),magnetic resonance imaging(MRI)and near-infrared fluorescent imaging(NIRF)probes,for the molecular imaging of tumors.Among them,an integrinα6-targeted SPECT probe has been proven to be safe and efficient for detecting breast cancer in the first-in-human pilot study.Moreover,we have developed integrinα6-targeted therapeutic strategies for the treatment of tumors.In this review,we highlight the latest progress in integrinα6-targeted tumor theranostics.
基金supported by grants from the Scientific Research Foundation for Young Doctors of the Second Affiliated Hospital,Army Medical University(2022YQB041)the Chongqing Natural Science Foundation(CSTB2024NSCQ-MSX0924 and CSTB2024NSCQ-MSX0909).
文摘The angiogenic response is essential for the repair of ischemic brain tissue.Integrin α6(Itga6)expression has been shown to increase under hypoxic conditions and is expressed exclusively in vascular structures;however,its role in post-ischemic angiogenesis remains poorly understood.In this study,we demonstrate that mice with endothelial cell-specific knockout of Itga6 exhibit reduced neovascularization,reduced pericyte coverage on microvessels,and accelerated breakdown of microvascular integrity in the peri-infarct area.In vitro,endothelial cells with ITGA6 knockdown display reduced proliferation,migration,and tube-formation.Mechanistically,we demonstrated that ITGA6 regulates post-stroke angiogenesis through the PI3K/Akt-eNOS-VEGFA axis.Importantly,the specific overexpression of Itga6 in endothelial cells significantly enhanced neovascularization and enhanced the integrity of microvessels,leading to improved functional recovery.Our results suggest that endothelial cell Itga6 plays a crucial role in key steps of post-stroke angiogenesis,and may represent a promising therapeutic target for promoting recovery after stroke.
