An in vitro model of breast cancer metastatic niche priming

Abstract

Metastatic breast cancer is responsible for around 11,500 deaths a year in the UK. The primary tumour likely plays a major role in priming the distant site for metastasis and crosstalk between primary and metastatic sites may be essential for secondary tumour growth. We have developed a novel in vitro model in which we can further study these interactions; evaluating niche priming and cancer cell conditioning as well as assessing their influence on cell homing and colonisation. In this paper we describe a model that we believe adds to the array of in vitro tools available to study various stages of the metastatic cascade, offering a unique opportunity to assess bidirectional, primary to niche interactions in vitro. We show that proliferation, migration and chemotaxis, and stem cell activity are altered in both cancer cell lines and in lung epithelial cells following linked, fluidic culture. Changes in cell homing and colonisation can be modelled in cell lines and within viable lung tissue explants taken from mice, with breast cancer cells settling and growing within the lung epithelial cells and tissue explants over 7 days. The colonisation/growth of cells injected into the system closely represents that seen following tail vein injection and cancer cells can be seen to settle and grow within the lung epithelial cells.