A novel labelling strategy enables spatial resolution of metastatic niche cellular composition and uncovers lung stem cell activity proximal to breast cancer

ABSTRACT: Cancer cell behaviour is strongly influenced by the surrounding cellular environment, making the characterization of the local tumour microenvironment (or niche) a fundamental question in tumour biology. To date, a direct investigation of the early cellular changes induced by metastatic cells within the surrounding tissue is difficult to achieve, especially at early micro-metastatic stages and for low frequency niche populations. Here we present the strategy whereby metastatic cancer cells release a cell-penetrating fluorescent protein that is efficiently taken up by neighbouring cells, allowing spatial identification of the local metastatic cellular environment within the whole tissue. Notably, this strategy can be used to follow metastatic niches from early micro-metastasis to late macro-metastasis, allowing temporal resolution. Moreover, the presence of low represented niche cells can be detected and characterized among the bulk tissue. To highlight its potential, we have used this niche-labelling strategy to study the lung metastatic environment of breast cancer cells. We uncover the presence of lung parenchymal cells within the metastatic niche where lung epithelial cells show stem cell-like features with expression of lung progenitor markers, multi-lineage differentiation potential and self-renewal activity. Moreover, lung epithelial cells can be directly perturbed by cancer cells in ex vivo co-culture assays and support their growth. In summary, here we describe a novel labelling system that enables spatial resolution of the metastatic microenvironment and provide evidence that the tissue cellular environment surrounding metastatic growth is characterized by undifferentiated features. The data highlight the significant potential of this method as a platform for new discoveries.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Lung

SUBMITTER: Ivonne Heinze  

LAB HEAD: Alessandro Ori

PROVIDER: PXD010597 | Pride | 2019-08-21

REPOSITORIES: Pride