The role of stromal fibroblasts in lung carcinogenesis: a target for chemoprevention?

The tumour microenvironment plays an essential role in the development and spread of cancers. Tumour cells interact with the surrounding extracellular matrix (ECM), embedded within which, are a variety of non-cancer cells including cells of the vasculature, immune system and fibroblasts. The essential role of fibroblasts in the cultivation and maintenance of an environment in which tumour cells are able to maintain their aggressive phenotypic traits is becoming increasingly well documented. Cancer-associated fibroblasts are able to secrete a vast array of ECM-modulating factors, meaning that they have potential for a functional role in every step of the carcinogenic process. In particular, they are likely to have a role in early tumour-initiating inflammatory events, and so may provide a potential target for chemopreventive intervention. This review summarises the known interactions between lung tumour cells and surrounding reactive fibroblasts, highlighting the need to further investigate cancer-associated fibroblasts as therapeutic targets in lung cancer chemoprevention strategies.