title: Bioengineered implantable scaffolds as a tool to study stromal-derived factors in metastatic cancer models.
abstract: Modeling the hematogenous spread of cancer cells to distant organs poses one of the greatest challenges in the study of human metastasis. Both tumor cell-intrinsic properties as well as interactions with reactive stromal cells contribute to this process, but identification of relevant stromal signals has been hampered by the lack of models allowing characterization of the metastatic niche. Here, we describe an implantable bioengineered scaffold, amenable to in vivo imaging, ex vivo manipulation, and serial transplantation for the continuous study of human metastasis in mice. Orthotopic or systemic inoculation of tagged human cancer cells into the mouse leads to the release of circulating tumor cells into the vasculature, which seed the scaffold, initiating a metastatic tumor focus. Mouse stromal cells can be readily recovered and profiled, revealing differential expression of cytokines, such as IL1β, from tumor-bearing versus unseeded scaffolds. Finally, this platform can be used to test the effect of drugs on suppressing initiation of metastatic lesions. This generalizable model to study cancer metastasis may thus identify key stromal-derived factors with important implications for basic and translational cancer research.
authors.affiliation: Cancer Center and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bersani
authors.affiliation: Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospitals for Children, Boston, Massachusetts.
authors.forename: Jungwoo
authors.initials: J
authors.lastname: Lee
authors.affiliation: Cancer Center and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts. Howard Hughes Medical Institute, Chevy Chase, Maryland.
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.affiliation: Cancer Center and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.
authors.forename: Robert
authors.initials: R
authors.lastname: Morris
authors.affiliation: Cancer Center and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.
authors.forename: Rushil
authors.initials: R
authors.lastname: Desai
authors.affiliation: Cancer Center and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Ramaswamy
authors.affiliation: Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospitals for Children, Boston, Massachusetts.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Toner
authors.affiliation: Cancer Center and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts. Howard Hughes Medical Institute, Chevy Chase, Maryland. haber@helix.mgh.harvard.edu biju_parekkadan@hms.harvard.edu.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Haber
authors.affiliation: Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospitals for Children, Boston, Massachusetts. Harvard Stem Cell Institute, Boston, Massachusetts. haber@helix.mgh.harvard.edu biju_parekkadan@hms.harvard.edu.
authors.forename: Biju
authors.initials: B
authors.lastname: Parekkadan
mesh_terms: D000818:Animals; D001698:Biomedical Engineering / Q000379:methods; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis; D051379:Mice; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D054457:Tissue Scaffolds
chemical_list: C587672:IL1B protein, mouse; D053583:Interleukin-1beta