Modeling metastasis biology and therapy in real time in the mouse lung

Arnulfo Mendoza, Sung Hyeok Hong, Tanasa Osborne, Mohammed A. Khan, Kirk Campbell, Joseph Briggs, Ananth Eleswarapu, Lauren Buquo, Ling Ren, Stephen M. Hewitt, El H. Dakir, Susan Garfield, Renard Walker, Glenn Merlino, Jeffrey E. Green, Kent W. Hunter, Lalage M. Wakefield, Chand Khanna

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Pulmonary metastasis remains the leading ca use of death for cancer patients. Opportunities to improve treatment outcomes for patients require new methods to study and view the biology of metastatic progression. Here, we describe an ex vivo pulmonary metastasis assay (PuMA) in which the metastatic progression of GFP-expressing cancer cells, from a single cell to the formation of multicellular colonies, in the mouse lung microenvironment was assessed in real time for up to 21 days. The biological validity of this assay was confirmed by its prediction of the in vivo behavior of a variety of high- and low-metastatic human and mouse cancer cell lines and the discrimination of tumor microenvironments in the lung that were most permissive to metastasis. Using this approach, we provide what we believe to be new insights into the importance of tumor cell interactions with the stromal components of the lung microenvironment. Finally, the translational utility of this assay was demonstrated through its use in the evaluation of therapeutics at discrete time points during metastatic progression. We believe that this assay system is uniquely capable of advancing our understanding of both metastasis biology and therapeutic strategies.

Original languageEnglish (US)
Pages (from-to)2979-2988
Number of pages10
JournalJournal of Clinical Investigation
Volume120
Issue number8
DOIs
StatePublished - Aug 2 2010
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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