Molecular biology of peritoneal carcinomatosis

Abstract

Peritoneal carcinomatosis can be thought of as a sequence of events that together form a peritoneal metastatic cascade. Presently our understanding of the molecular mediators that orchestrate this cascade is ill-understood. Initial tumour-mesothelial interaction appears to involve several adhesion molecules, including CD44, the Selectins, and various leukocyte associated antigens. The exact molecules involved are probably determined by the nature of the metastatic tumour cell. Invasion of the mesothelial monolayer appears to occur by tumour-induced mesothelial apoptosis, at least in part via the Fas/FasL system, although invasion between intercellular spaces may also play a role. Adhesion to the submesothelial connective tissue is mediated by tumour integrin binding. The peritoneal stromal tissue appears to be a favourable host for tumour proliferation, providing a rich source of growth factors and chemokines known to be involved in tumour metastasis. Angiogenesis is vital to peritoneal tumour growth and although the peritoneum has a well developed blood supply the angiogenic events specific to peritoneal tumour metastasis remain to be elucidated. Further investigation is required to unravel the complexities of the peritoneal metastatic cascade and this will inevitably open up many avenues for novel therapeutic manipulation and disease modulation.