The multiple roles of tumour stroma.

Since the work of Judah Folkman in the 1970s demonstrating the importance of vascularization on tumour growth the many roles played by tumour stroma have been demonstrated. Vascular endothelial growth factor/vascular permeability factor appears to be the main in vivo inducer of both stromal blood vessels and other components of the tumour stroma. Its action is probably mediated through its strong and long-lasting effect on microvascular permeability leading to fibrin extravasation and organisation ("tumours are wounds that do not heal"). During tumour invasion, stromal fibroblasts participate in the degradation of the extracellular matrix (ECM) by secreting matrix degrading proteases as well as their downstream-activators. Stroma derived factors such as scatter factor/hepatocyte growth factor as well as interactions between neoplastic cells and the ECM can play a role in both tumour cell migration and proliferation. The ECM may also act as a reservoir for growth factors. A novel transcription factor encoded by the c-ets 1 proto-oncogene is likely to be involved in the transcriptional regulation of both tumour vascularization and invasion. This contribution summarizes recent developments in the tumour stroma field.