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

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

SUBMITTER: Shen K 

PROVIDER: S-EPMC4261930 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature