Our studies are aimed at understanding the function of cancer-associated fibroblasts in breast cancer invasion and in particular the role of stromal transmembrane receptors

Our laboratory has a long-standing interest in the role of stromal cells in tumour progression with an emphasis on the interaction between extracellular matrix proteins and stromal transmembrane receptors, such as CD44, endosialin and Endo180. The latter is a recently described recycling transmembrane receptor, which binds and delivers collagens for intracellular lysosomal degradation (Wienke et al., 2003; Sturge et al., 2006).

Endo180 is normally expressed on stromal fibroblasts, though some tumour types gain expression of this receptor. For example, we have demonstrated that the expression of Endo180 on a subset of invasive basal-like breast cancers was an independent prognostic indicator of reduced disease-free survival and associated with an increased collagen turnover (Wienke et al., 2007).

Our current studies are focused on elucidating how receptors such as Endo180 that are expressed on stromal fibroblasts, aid the invasion of tumour cells into their surrounding tissue by remodelling the extracellular matrix components. For this we are employing 3D in vitro co-culture models as well as syngeneic tumour models in mice with targeted deletions in key stromal receptors.