title: Enhanced Survival with Implantable Scaffolds That Capture Metastatic Breast Cancer Cells In Vivo.
abstract: The onset of distant organ metastasis from primary breast cancer marks the transition to a stage IV diagnosis. Standard imaging modalities often detect distant metastasis when the burden of disease is high, underscoring the need for improved methods of detection to allow for interventions that would impede disease progression. Here, microporous poly(ε-caprolactone) scaffolds were developed that capture early metastatic cells and thus serve as a sentinel for early detection. These scaffolds were used to characterize the dynamic immune response to the implant spanning the acute and chronic foreign body response. The immune cell composition had stabilized at the scaffold after approximately 1 month and changed dramatically within days to weeks after tumor inoculation, with CD11b(+)Gr1(hi)Ly6C(-) cells having the greatest increase in abundance. Implanted scaffolds recruited metastatic cancer cells that were inoculated into the mammary fat pad in vivo, which also significantly reduced tumor burden in the liver and brain. Additionally, cancer cells could be detected using a label-free imaging modality termed inverse spectroscopic optical coherence tomography, and we tested the hypothesis that subsequent removal of the primary tumor after early detection would enhance survival. Surgical removal of the primary tumor following cancer cell detection in the scaffold significantly improved disease-specific survival. The enhanced disease-specific survival was associated with a systemic reduction in the CD11b(+)Gr1(hi)Ly6C(-) cells as a consequence of the implant, which was further supported by Gr-1 depletion studies. Implementation of the scaffold may provide diagnostic and therapeutic options for cancer patients in both the high-risk and adjuvant treatment settings. Cancer Res; 76(18); 5209-18. ©2016 AACR.
authors.affiliation: Department of Chemical and Biological Engineering, University of Alabama, Tuscaloosa, Alabama.
authors.forename: Shreyas S
authors.initials: SS
authors.lastname: Rao
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
authors.forename: Grace G
authors.initials: GG
authors.lastname: Bushnell
authors.affiliation: Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Samira M
authors.initials: SM
authors.lastname: Azarin
authors.affiliation: Department of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois.
authors.forename: Graham
authors.initials: G
authors.lastname: Spicer
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Aguado
authors.affiliation: Weinberg College of Arts and Sciences, Northwestern University, Evanston, Illinois.
authors.forename: Jenna R
authors.initials: JR
authors.lastname: Stoehr
authors.affiliation: Department of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Jiang
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Evanston, Illinois.
authors.forename: Vadim
authors.initials: V
authors.lastname: Backman
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan. Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan. ldshea@umich.edu jjeruss@med.umich.edu.
authors.forename: Lonnie D
authors.initials: LD
authors.lastname: Shea
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan. Department of Surgery, University of Michigan, Ann Arbor, Michigan. ldshea@umich.edu jjeruss@med.umich.edu.
authors.forename: Jacqueline S
authors.initials: JS
authors.lastname: Jeruss
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009362:Neoplasm Metastasis / Q000473:pathology*; D011091:Polyesters; D054457:Tissue Scaffolds; D041623:Tomography, Optical Coherence
chemical_list: D011091:Polyesters; C016240:polycaprolactone