Figure 5

The figure summarises the main molecular and physical events that contribute to peritoneal metastatic niche development and ECM remodelling. Cancer cells exert their effect on the peritoneal metastasis microenvironment through three main modes: (1) the release of specific growth factors, such as TGFβ, leading to the recruitment of resident fibroblasts and their activation into CAF. (2) The production of exosomes that trigger the microenvironment and mediate the activation of CAFs and the polarisation of macrophages into M2 phenotype. (3) The production of pro-inflammatory cytokines, which contribute to enhancing the activity of CAFs and M2 macrophages by promoting the TGFβ pathway in a paracrine manner. Together, these events contribute to the production and/or deposition of naïve ECM and the concomitant increase in ECM stiffness, both around the site of injury and at distant sites in the peritoneal cavity, which may be a sign of disease progression.