Resolving cancer–stroma interfacial signalling and interventions with micropatterned tumour–stromal assays

Keyue Shen (), Samantha Luk, Daniel F. Hicks, Jessica S. Elman, Stefan Bohr, Yoshiko Iwamoto, Ryan Murray, Kristen Pena, Fangjing Wang, Erkin Seker, Ralph Weissleder, Martin L. Yarmush, Mehmet Toner, Dennis Sgroi and Biju Parekkadan ()
Additional contact information
Keyue Shen: Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospitals for Children
Samantha Luk: Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospitals for Children
Daniel F. Hicks: Molecular Pathology Unit, Massachusetts General Hospital
Jessica S. Elman: Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospitals for Children
Stefan Bohr: Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospitals for Children
Yoshiko Iwamoto: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School
Ryan Murray: Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospitals for Children
Kristen Pena: Massachusetts Institute of Technology
Fangjing Wang: Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospitals for Children
Erkin Seker: Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospitals for Children
Ralph Weissleder: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School
Martin L. Yarmush: Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospitals for Children
Mehmet Toner: Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospitals for Children
Dennis Sgroi: Molecular Pathology Unit, Massachusetts General Hospital
Biju Parekkadan: Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospitals for Children

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: Abstract Tumour–stromal interactions are a determining factor in cancer progression. In vivo, the interaction interface is associated with spatially resolved distributions of cancer and stromal phenotypes. Here, we establish a micropatterned tumour–stromal assay (μTSA) with laser capture microdissection to control the location of co-cultured cells and analyse bulk and interfacial tumour–stromal signalling in driving cancer progression. μTSA reveals a spatial distribution of phenotypes in concordance with human oestrogen receptor-positive (ER+) breast cancer samples, and heterogeneous drug activity relative to the tumour–stroma interface. Specifically, an unknown mechanism of reversine is shown in targeting tumour–stromal interfacial interactions using ER+ MCF-7 breast cancer and bone marrow-derived stromal cells. Reversine suppresses MCF-7 tumour growth and bone metastasis in vivo by reducing tumour stromalization including collagen deposition and recruitment of activated stromal cells. This study advocates μTSA as a platform for studying tumour microenvironmental interactions and cancer field effects with applications in drug discovery and development.

Date: 2014
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DOI: 10.1038/ncomms6662

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