The complexities of breast cancer desmoplasia

One of the features of many carcinomas, particularly breast, is the presence of a dense collagenous stroma, the so-called desmoplastic response, which can be responsible for the clinical presentation of a tumour as a 'lump'. Although studies in the 1950s proposed that the desmoplasia represented the condensation of pre-existing collagen [1] there is now good evidence that the collagen is synthesised by myofibroblasts present in the interstitium [2,3]. Several mechanisms that result in myofibroblast activation and collagen synthesis have been proposed. These include immune cytokine mechanisms and microvascular injury [4], with features analogous to wound healing [5], and paracrine activation of myofibroblasts by growth factors released by tumour cells [6,7]. Various growth factors, such as transforming growth factor (TGF)-α, TGF-β, insulin-like growth factor (IGF)-I, IGF-II and platelet-derived growth factor (PDGF), have been identified that are secreted by cancer cells and can stimulate stromal cells [8,9,10,11]. It is evident that complex epithelial-stromal cell interactions exist. Many of the data supporting this come from studies in vitro, which by their nature are generally short term.Histological examination of a range of primary breast carcinomas shows that the stromal response can vary from being predominantly cellular (fibroblasts/myofibroblasts) with little collagenous tissue, through to a dense collagen stroma with apparently few stromal cells. The obvious question is why there are these differences and how the findings in primary breast carcinomas relate to cell-based co-culture systems in vitro. There is also a need to understand the nature of the role of the stromal desmoplasia in cancer progression: does it vary with the transition from disease in situ to invasive disease?To determine the mechanisms of development of desmoplasia a more appropriate model system is required. Previous studies of human tumour xenografts in 'nude' mice have shown a lack of