A team of scientists led by researchers at the Wistar Institute has now identified a critical role for fibroblast activation protein (FAP), expressed by TAFs, in promoting tumour growth in mice. FAP is a type II cell surface serine protease expressed predominantly by fibroblastic cells in areas of active tissue remodelling such as tumour stroma, fibrosis, or healing wounds. FAP is a member of the post-proline dipeptidyl aminopeptidase family, sharing the highest similarity with dipeptidyl peptidase IV (DPPIV) but, unlike DPPIV, FAP is not found in benign lesions or normal adult tissues.The team found that the enzymatic activity of endogenous FAP promoted tumour growth in mouse models of lung and colon cancer and, moreover, that genetic deletion of FAP expression, or pharmacological inhibition of FAP activity using PT630, was able to significantly inhibit tumour cell proliferation. Inhibition of FAP activity was further shown to disrupt the organisation of collagen fibres in the extracellular matrix and decrease blood vessel density in tumours.
FAP is expressed in 90% of solid tumours and the study, which is published in the Journal of Clinical Investigation, suggests that therapies that target stromal cells could increase the effectiveness of cancer cell-targeted therapies for solid tumours.