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Reactive astrocytic S1P3 signaling modulates the blood-tumor barrier in brain metastases.
Gril, Brunilde; Paranjape, Anurag N; Woditschka, Stephan; Hua, Emily; Dolan, Emma L; Hanson, Jeffrey; Wu, Xiaolin; Kloc, Wojciech; Izycka-Swieszewska, Ewa; Duchnowska, Renata; Peksa, Rafal; Biernat, Wojciech; Jassem, Jacek; Nayyar, Naema; Brastianos, Priscilla K; Hall, O Morgan; Peer, Cody J; Figg, William D; Pauly, Gary T; Robinson, Christina; Difilippantonio, Simone; Bialecki, Emilie; Metellus, Philippe; Schneider, Joel P; Steeg, Patricia S.
Afiliación
  • Gril B; Women's Malignancies Branch, CCR, NCI, Bethesda, 20892, MD, USA. grilbrun@mail.nih.gov.
  • Paranjape AN; Women's Malignancies Branch, CCR, NCI, Bethesda, 20892, MD, USA.
  • Woditschka S; Women's Malignancies Branch, CCR, NCI, Bethesda, 20892, MD, USA.
  • Hua E; Department of Biology and Marine Biology, University of North Carolina at Wilmington, 601 South College Road, Wilmington, NC, 28403, USA.
  • Dolan EL; Women's Malignancies Branch, CCR, NCI, Bethesda, 20892, MD, USA.
  • Hanson J; Women's Malignancies Branch, CCR, NCI, Bethesda, 20892, MD, USA.
  • Wu X; Laboratory of Pathology, CCR, NCI, Bethesda, 20892, MD, USA.
  • Kloc W; Genomics Laboratory, Frederick National Laboratory for Cancer Research, Frederick, 21702, MD, USA.
  • Izycka-Swieszewska E; Department of Neurology & Neurosurgery, Varmia & Masuria University, Olsztyn, 10-719, Poland.
  • Duchnowska R; Department of Neurosurgery, Copernicus Hospital Gdansk, Gdansk, 80-803, Poland.
  • Peksa R; Department of Pathology & Neuropathology, Medical University of Gdansk, Gdansk, 80-210, Poland.
  • Biernat W; Department of Pathomorphology, Copernicus Hospital Gdansk, Gdansk, 80-803, Poland.
  • Jassem J; Department of Oncology, Military Institute of Medicine, Warsaw, 04-141, Poland.
  • Nayyar N; Department of Pathology, Medical University of Gdansk, 7 Debinki St, 80-211, Gdansk, Poland.
  • Brastianos PK; Department of Pathology, Medical University of Gdansk, 7 Debinki St, 80-211, Gdansk, Poland.
  • Hall OM; Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, 80-211, Poland.
  • Peer CJ; Division of Neuro-Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, 02114, MA, USA.
  • Figg WD; Division of Neuro-Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, 02114, MA, USA.
  • Pauly GT; Genitourinary Malignancies Branch, CCR, NCI, Bethesda, 20892, MD, USA.
  • Robinson C; Genitourinary Malignancies Branch, CCR, NCI, Bethesda, 20892, MD, USA.
  • Difilippantonio S; Genitourinary Malignancies Branch, CCR, NCI, Bethesda, 20892, MD, USA.
  • Bialecki E; Chemical Biology Laboratory, CCR, NCI, Frederick, 21702, MD, USA.
  • Metellus P; Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, Frederick, 21702, MD, USA.
  • Schneider JP; Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, Frederick, 21702, MD, USA.
  • Steeg PS; Département de Neurochirurgie, Hôpital Privé Clairval, Ramsay Général de Santé, Marseille, 13009, France.
Nat Commun ; 9(1): 2705, 2018 07 13.
Article en En | MEDLINE | ID: mdl-30006619
Brain metastases are devastating complications of cancer. The blood-brain barrier (BBB), which protects the normal brain, morphs into an inadequately characterized blood-tumor barrier (BTB) when brain metastases form, and is surrounded by a neuroinflammatory response. These structures contribute to poor therapeutic efficacy by limiting drug uptake. Here, we report that experimental breast cancer brain metastases of low- and high permeability to a dextran dye exhibit distinct microenvironmental gene expression patterns. Astrocytic sphingosine-1 phosphate receptor 3 (S1P3) is upregulated in the neuroinflammatory response of the highly permeable lesions, and is expressed in patients' brain metastases. S1P3 inhibition functionally tightens the BTB in vitro and in vivo. S1P3 mediates its effects on BTB permeability through astrocytic secretion of IL-6 and CCL2, which relaxes endothelial cell adhesion. Tumor cell overexpression of S1P3 mimics this pathway, enhancing IL-6 and CCL-2 production and elevating BTB permeability. In conclusion, neuroinflammatory astrocytic S1P3 modulates BTB permeability.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Barrera Hematoencefálica / Regulación Neoplásica de la Expresión Génica / Astrocitos / Receptores de Lisoesfingolípidos / Neoplasias de la Mama Triple Negativas Límite: Animals / Female / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Barrera Hematoencefálica / Regulación Neoplásica de la Expresión Génica / Astrocitos / Receptores de Lisoesfingolípidos / Neoplasias de la Mama Triple Negativas Límite: Animals / Female / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido