Figure 2.
Illustration of SMT and TOFT models: (a) The SMT posits that carcinogens lead to mutations in the cellular DNA of epithelial cells, leading to propagation of cells carrying advantageous mutations. Paracrine factors secreted by the growing tumour alter the tumour stroma. The altered or ‘activated’ stroma in turn contributes to cancer progression, enabling a conducive environment for tumour cell invasion and metastasis. (b) The TOFT model predicts that carcinogens affect the stroma, leading to altered cell–ECM and cell–cell interactions in the epithelium, which then results in tumour formation in the epithelium.