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, Biju Parekkadan

Research output: Contribution to journalArticle

25 Scopus citations

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 (Î 1/4TSA) with laser capture microdissection to control the location of co-cultured cells and analyse bulk and interfacial tumour-stromal signalling in driving cancer progression. Î 1/4TSA 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 Î 1/4TSA as a platform for studying tumour microenvironmental interactions and cancer field effects with applications in drug discovery and development.

Original languageEnglish (US)
Article number5662
JournalNature Communications
Volume5
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Shen, K., Luk, S., Hicks, D. F., Elman, J. S., Bohr, S., Iwamoto, Y., Murray, R., Pena, K., Wang, F., Seker, E., Weissleder, R., Yarmush, M. L., Toner, M., Sgroi, D., & Parekkadan, B. (2014). Resolving cancer-stroma interfacial signalling and interventions with micropatterned tumour-stromal assays. Nature Communications, 5, [5662]. https://doi.org/10.1038/ncomms6662