Portal de Periódicos da CAPES

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

2014; Nature Portfolio; Volume: 5; Issue: 1 Linguagem: Inglês

10.1038/ncomms6662

2041-1723

K. Robert Shen, Samantha Luk, Daniel F. Hicks, Jessica S. Elman, Stefan Bohr, Yoshiko Iwamoto, Ryan Murray, Kristen C. Peña, Fangjing Wang, Erkin Şeker, Ralph Weissleder, Martin L. Yarmush, Mehmet Toner, Dennis C. Sgroi, Biju Parekkadan,

Cellular Mechanics and Interactions

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.