Biomaterial Scaffolds as Pre-metastatic Niche Mimics Systemically Alter the Primary Tumor and Tumor Microenvironment

Brian A. Aguado, Rachel M. Hartfield, Grace G. Bushnell, Joseph T. Decker, Samira M. Azarin, Dhaval Nanavati, Matthew John Schipma, Shreyas S. Rao, Robert S. Oakes, Yining Zhang, Jacqueline S. Jeruss, Lonnie D. Shea*

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number1700903
JournalAdvanced Healthcare Materials
Volume7
Issue number10
DOIs
StatePublished - May 23 2018

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Tumor Microenvironment
Biocompatible Materials
Biomaterials
Scaffolds
Tumors
Neoplasms
Cells
Conditioned Culture Medium
Neoplasm Metastasis
Decorin
Surgery
Chemokine CCL2
Transcription factors
Macrophages
Transcription Factors
Scaffolds (biology)
Phenotype

Keywords

  • biomaterial
  • immunomodulation
  • metastasis
  • pre-metastatic niche
  • tumor microenvironment

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

Cite this

Aguado, B. A., Hartfield, R. M., Bushnell, G. G., Decker, J. T., Azarin, S. M., Nanavati, D., ... Shea, L. D. (2018). Biomaterial Scaffolds as Pre-metastatic Niche Mimics Systemically Alter the Primary Tumor and Tumor Microenvironment. Advanced Healthcare Materials, 7(10), [1700903]. https://doi.org/10.1002/adhm.201700903
Aguado, Brian A. ; Hartfield, Rachel M. ; Bushnell, Grace G. ; Decker, Joseph T. ; Azarin, Samira M. ; Nanavati, Dhaval ; Schipma, Matthew John ; Rao, Shreyas S. ; Oakes, Robert S. ; Zhang, Yining ; Jeruss, Jacqueline S. ; Shea, Lonnie D. / Biomaterial Scaffolds as Pre-metastatic Niche Mimics Systemically Alter the Primary Tumor and Tumor Microenvironment. In: Advanced Healthcare Materials. 2018 ; Vol. 7, No. 10.
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abstract = "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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Aguado, BA, Hartfield, RM, Bushnell, GG, Decker, JT, Azarin, SM, Nanavati, D, Schipma, MJ, Rao, SS, Oakes, RS, Zhang, Y, Jeruss, JS & Shea, LD 2018, 'Biomaterial Scaffolds as Pre-metastatic Niche Mimics Systemically Alter the Primary Tumor and Tumor Microenvironment', Advanced Healthcare Materials, vol. 7, no. 10, 1700903. https://doi.org/10.1002/adhm.201700903

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 John; Rao, Shreyas S.; Oakes, Robert S.; Zhang, Yining; Jeruss, Jacqueline S.; Shea, Lonnie D.

In: Advanced Healthcare Materials, Vol. 7, No. 10, 1700903, 23.05.2018.

Research output: Contribution to journalArticle

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T1 - Biomaterial Scaffolds as Pre-metastatic Niche Mimics Systemically Alter the Primary Tumor and Tumor Microenvironment

AU - Aguado, Brian A.

AU - Hartfield, Rachel M.

AU - Bushnell, Grace G.

AU - Decker, Joseph T.

AU - Azarin, Samira M.

AU - Nanavati, Dhaval

AU - Schipma, Matthew John

AU - Rao, Shreyas S.

AU - Oakes, Robert S.

AU - Zhang, Yining

AU - Jeruss, Jacqueline S.

AU - Shea, Lonnie D.

PY - 2018/5/23

Y1 - 2018/5/23

N2 - 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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KW - biomaterial

KW - immunomodulation

KW - metastasis

KW - pre-metastatic niche

KW - tumor microenvironment

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