Cell Biology of Cancer Peritoneal Metastasis: Multiclonal Seeding and Peritoneal Tumor Microenvironment

Peritoneal metastasis, also known as peritoneal dissemination or carcinomatosis, refers to the spread of cancer to the peritoneum that lines the abdominal and pelvic cavities and covers the abdominal organs. Peritoneal metastasis typically occurs in advanced cancers of abdominal origin, most commonly gastrointestinal and gynecological cancers. Conventional chemotherapy has limited efficacy, and no effective molecular-targeted therapy is currently available for peritoneal metastasis. As a result, peritoneal metastasis is associated with poor outcomes and significantly reduced quality of life in patients with advanced cancers. This is largely due to a limited understanding of the molecular and cellular mechanisms underlying peritoneal metastasis. However, recent studies employing innovative approaches have provided novel insights into the mechanisms of peritoneal metastasis, contributing to the development of novel therapeutic strategies. In this review, we summarize recent findings on the cell biological aspects of peritoneal metastasis and potential therapeutic target molecules. In particular, we emphasize the importance of cancer cell clustering within the abdominal cavity, which drives multiclonal peritoneal seeding. We also focus on the interactions of cancer cells with mesothelial cells and cancer-associated fibroblasts within the peritoneal tumor microenvironment.