We have found that tumour cells could activate ECs through VEGF and MMPs secretion, which is in agreement with previous reports (Gialeli et al., 2010) and with our data showing that MMPs are involved in TNFα-induced VE-cadherin cleavage.19 It can be assumed that MMPs found in the tumour microenvironment could participate in ECs remodeling by inducing VE-cadherin cleavage, as it was already shown for the cleavage of several cell surface proteins.33 Our working hypothesis is illustrated in Fig. 6. Here, TNF is linked to neoplasm.