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Biomaterial Scaffolds as Pre-metastatic Niche Mimics Systemically Alter the Primary Tumor and Tumor Microenvironment.
Aguado, Brian A; Hartfield, Rachel M; Bushnell, Grace G; Decker, Joseph T; Azarin, Samira M; Nanavati, Dhaval; Schipma, Matthew J; Rao, Shreyas S; Oakes, Robert S; Zhang, Yining; Jeruss, Jacqueline S; Shea, Lonnie D.
Afiliación
  • Aguado BA; Department of Biomedical Engineering, Simpson Querrey Institute for BioNanotechnology, Northwestern University, Evanston, IL, 60208, USA.
  • Hartfield RM; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48105, USA.
  • Bushnell GG; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48105, USA.
  • Decker JT; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48105, USA.
  • Azarin SM; Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN, 55455, USA.
  • Nanavati D; Proteomics Core Facility, Northwestern University, Chicago, IL, 60611, USA.
  • Schipma MJ; NUSeq Core Facility, Northwestern University, Chicago, IL, 60611, USA.
  • Rao SS; Department of Chemical and Biological Engineering, University of Alabama, Tuscaloosa, AL, 35487, USA.
  • Oakes RS; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48105, USA.
  • Zhang Y; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48105, USA.
  • Jeruss JS; Department of Surgery, University of Michigan, Ann Arbor, MI, 48105, USA.
  • Shea LD; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48105, USA.
Adv Healthc Mater ; 7(10): e1700903, 2018 05.
Article en En | MEDLINE | ID: mdl-29521008
Primary tumor (PT) immune cells and pre-metastatic niche (PMN) sites are critical to metastasis. Recently, synthetic biomaterial scaffolds used as PMN mimics are shown to capture both immune and metastatic tumor cells. Herein, studies are performed to investigate whether the scaffold-mediated redirection of immune and tumor cells would alter the primary tumor microenvironment (TME). Transcriptomic analysis of PT cells from scaffold-implanted and mock-surgery mice identifies differentially regulated pathways relevant to invasion and metastasis progression. Transcriptomic differences are hypothesized to result from scaffold-mediated modulations of immune cell trafficking and phenotype in the TME. Culturing tumor cells with conditioned media generated from PT immune cells of scaffold-implanted mice decrease invasion in vitro more than two-fold relative to mock surgery controls and reduce activity of invasion-promoting transcription factors. Secretomic characterization of the conditioned media delineates interactions between immune cells in the TME and tumor cells, showing an increase in the pan-metastasis inhibitor decorin and a concomitant decrease in invasion-promoting chemokine (C-C motif) ligand 2 (CCL2) in scaffold-implanted mice. Flow cytometric and transcriptomic profiling of PT immune cells identify phenotypically distinct tumor-associated macrophages (TAMs) in scaffold-implanted mice, which may contribute to an invasion-suppressive TME. Taken together, this study demonstrates biomaterial scaffolds systemically influence metastatic progression through manipulation of the TME.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Materiales Biocompatibles / Neoplasias de la Mama / Materiales Biomiméticos / Andamios del Tejido / Microambiente Tumoral / Neoplasias Mamarias Experimentales Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Adv Healthc Mater Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Materiales Biocompatibles / Neoplasias de la Mama / Materiales Biomiméticos / Andamios del Tejido / Microambiente Tumoral / Neoplasias Mamarias Experimentales Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Adv Healthc Mater Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania