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Mechanosensitive brain tumor cells construct blood-tumor barrier to mask chemosensitivity.
Chen, Xin; Momin, Ali; Wanggou, Siyi; Wang, Xian; Min, Hyun-Kee; Dou, Wenkun; Gong, Zheyuan; Chan, Jade; Dong, Weifan; Fan, Jerry J; Xiong, Yi; Talipova, Kamilia; Zhao, Hongyu; Chen, Yuki X; Veerasammy, Kelly; Fekete, Adam; Kumar, Sachin A; Liu, Hongwei; Yang, Qi; Son, Joe Eun; Dou, Zhengchao; Hu, Malini; Pardis, Parnian; Juraschka, Kyle; Donovan, Laura K; Zhang, Jiao; Ramaswamy, Vijay; Selvadurai, Hayden J; Dirks, Peter B; Taylor, Michael D; Wang, Lu-Yang; Hui, Chi-Chung; Abzalimov, Rinat; He, Ye; Sun, Yu; Li, Xuejun; Huang, Xi.
Afiliación
  • Chen X; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
  • Momin A; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 3E1
  • Wanggou S; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Neurosurgery, Xiangya Hospital, Central South University, Chan
  • Wang X; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
  • Min HK; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 3E1
  • Dou W; Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3G8, Canada.
  • Gong Z; Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3G8, Canada.
  • Chan J; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 3E1
  • Dong W; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 3E1
  • Fan JJ; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 3E1
  • Xiong Y; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Neurosurgery, Xiangya Hospital, Central South University, Chan
  • Talipova K; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
  • Zhao H; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Neurosurgery, Xiangya Hospital, Central South University, Chan
  • Chen YX; Advanced Science Research Center at the Graduate Center, City University of New York, New York, NY 10031, USA.
  • Veerasammy K; Advanced Science Research Center at the Graduate Center, City University of New York, New York, NY 10031, USA.
  • Fekete A; Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
  • Kumar SA; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
  • Liu H; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
  • Yang Q; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
  • Son JE; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
  • Dou Z; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 3E1, Canada.
  • Hu M; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
  • Pardis P; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
  • Juraschka K; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
  • Donovan LK; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
  • Zhang J; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
  • Ramaswamy V; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
  • Selvadurai HJ; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
  • Dirks PB; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 3E1
  • Taylor MD; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Surgery, University of Toronto, Toronto, ON M5S 3E1, Canada; D
  • Wang LY; Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Hui CC; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 3E1, Canada.
  • Abzalimov R; Advanced Science Research Center at the Graduate Center, City University of New York, New York, NY 10031, USA.
  • He Y; Advanced Science Research Center at the Graduate Center, City University of New York, New York, NY 10031, USA.
  • Sun Y; Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3G8, Canada.
  • Li X; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Electronic address: lxjneuro@cs
  • Huang X; Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 3E1
Neuron ; 111(1): 30-48.e14, 2023 01 04.
Article en En | MEDLINE | ID: mdl-36323321
ABSTRACT
Major obstacles in brain cancer treatment include the blood-tumor barrier (BTB), which limits the access of most therapeutic agents, and quiescent tumor cells, which resist conventional chemotherapy. Here, we show that Sox2+ tumor cells project cellular processes to ensheathe capillaries in mouse medulloblastoma (MB), a process that depends on the mechanosensitive ion channel Piezo2. MB develops a tissue stiffness gradient as a function of distance to capillaries. Sox2+ tumor cells perceive substrate stiffness to sustain local intracellular calcium, actomyosin tension, and adhesion to promote cellular process growth and cell surface sequestration of ß-catenin. Piezo2 knockout reverses WNT/ß-catenin signaling states between Sox2+ tumor cells and endothelial cells, compromises the BTB, reduces the quiescence of Sox2+ tumor cells, and markedly enhances the MB response to chemotherapy. Our study reveals that mechanosensitive tumor cells construct the BTB to mask tumor chemosensitivity. Targeting Piezo2 addresses the BTB and tumor quiescence properties that underlie treatment failures in brain cancer.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Beta Catenina Límite: Animals Idioma: En Revista: Neuron Asunto de la revista: NEUROLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Canadá
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Beta Catenina Límite: Animals Idioma: En Revista: Neuron Asunto de la revista: NEUROLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Canadá