Role of stromal fibroblasts in cancer: promoting or impeding?

The basement membrane, immune cells, capillaries, fibroblasts and extracellular matrix (ECM) constitute the tumour stroma, commonly referred to as the 'reactive stroma'. The fibroblasts from the initial stages of a tumour, as the main constituents of the reactive stroma, present a different phenotype from the normal fibroblasts and play a crucial role in tumour progression. This review presents the differences between normal and tumour stromal fibroblasts and analyzes the molecular mechanisms (which involve growth factors, ECM components, matrix metalloproteinases, integrins and cell adhesion molecules) in the complex interactions between stromal fibroblasts and tumour cells. To date, several examples of heterotypic interactions between tumour stromal fibroblasts and tumour cells have supported the hypothesis that the tumour stroma promotes the growth of the tumour mass, as well as invasion and metastasis. However, it remains possible that the stroma acts essentially as a local modulator to impede tumorigenesis at an early stage and that the desmoplastic response is a host defence reaction designed to confine the developing tumour. The latter hypothesis has largely been neglected. The review aims to give a broader view on the role of stromal fibroblasts in tumour growth, invasion and metastasis.