Fig. 1.

Changing patterns of metastatic spread with disease progression. a Cancer cells initially attach to milky spots where the stromal matrix is exposed, providing direct access to their preferred substrate, collagen I. The intact mesothelial layer discourages cancer cell attachment. b With disease progression and in response to increasing concentrations of inflammatory mediators, mesothelial cells retract and detach. The resulting exposure of the underlying ECM, with a discontinuous basement membrane, facilitates widespread peritoneal metastasis. TGF-β, released by cancer and inflammatory cells, stimulates myofibroblast transdifferentiation. c Metastasizing cancer cells, particularly those with a highly invasive, contractile phenotype, form compact spheroids in peritoneal fluid. This protects them against anoikis and chemotherapeutics. These spheroids attach to and invade the peritoneal matrix. The combination of their contractile and proteolytic capacities remodels the collagen I-rich matrix to facilitate stromal implantation and invasive growth