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Cancer Res. 2014 Dec 15;74(24):7229-38. doi: 10.1158/0008-5472.CAN-14-1809. Epub 2014 Oct 22.

Bioengineered implantable scaffolds as a tool to study stromal-derived factors in metastatic cancer models.

Author information

1
Cancer Center and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.
2
Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospitals for Children, Boston, Massachusetts.
3
Cancer Center and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts. Howard Hughes Medical Institute, Chevy Chase, Maryland.
4
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.
5
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.

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.

PMID:
25339351
PMCID:
PMC4267901
DOI:
10.1158/0008-5472.CAN-14-1809
[Indexed for MEDLINE]
Free PMC Article

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