Modeling metastasis biology and therapy in real time in the mouse lung.
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.
Mendoza
Arnulfo
A
Tumor and Metastasis Biology Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Hong
Sung-Hyeok
SH
Osborne
Tanasa
T
Khan
Mohammed A
MA
Campbell
Kirk
K
Briggs
Joseph
J
Eleswarapu
Ananth
A
Buquo
Lauren
L
Ren
Ling
L
Hewitt
Stephen M
SM
Dakir
El Habib
el H
Dakir
El-H
el-H
Garfield
Susan
S
Walker
Renard
R
Merlino
Glenn
G
Green
Jeffrey E
JE
Hunter
Kent W
KW
Wakefield
Lalage M
LM
Khanna
Chand
C
D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008815:Mice, Inbred Strains