Is carcinoma a mesenchymal disease? The role of the stromal microenvironment in carcinogenesis

SummaryMost research into the biology of carcinoma has focused on the epithelial cells therein; the inherent assumption has been that the tumour arises from epithelial cells ‘gone bad’, and that the surrounding stroma is simply an ‘innocent bystander’. However, there is increasing evidence that there is a complex interplay between tumour cells and their surrounding microenvironment, and that the latter may be just as important in determining the development and clinical behaviour of a given tumour. Similarly, traditional oncological practice has been predominantly aimed at a perceived ideal goal of killing all the tumour epithelial cells, with only a few recently developed therapies seeking to affect other components (such as tumour vasculature); but identifying stromal factors involved in tumour growth and survival may well lead to the development of novel therapies. This review examines current understanding of the interplay between tumour epithelial cells and their microenvironment, and enumerates various stromal factors which appear to play a role in tumour progression and/or metastasis.