Abstract
The human peritoneal cavity contains a small number of free cells of mesenchymal cell lineage. Intraperitoneal mesenchymal cells (PMC) play supportive roles in metastasis formation on the peritoneum. In this study, we found that PMC, when co-cultuerd with human gastric cancer cells, MKN45, enhanced the proliferation of MKN45 when cultured at low, but not high, cellular density. Also, PMC suppressed apoptotic cell death of MKN45 only under low density culture conditions. Time-lapse videoanalysis clearly demonstrated that PMC randomly migrated more vigorously than did MKN45, and strongly enhanced the migration behavior of co-cultured MKN45. In fact, the majority of MKN45 migrated together in direct physical contact with PMC, and the sum of migration lengths from original position of co-cultured MKN45 for 48 hours was approximately 10 times longer than that of MKN45 cultured alone. Our data suggest that enhanced migration can increase the chance of direct contact or positional proximity among sparcely distributed MKN45, which may bring survival advantages to tumor cells. This may be one of the important mechanisms of peritoneal metastasis, since only a small number of tumor cells are considered to be disseminated in the early step of metastasis formation on the peritoneum.
Highlights
The peritoneal cavity is a common target of metastatic gastrointestinal and ovarian cancer cells [1,2,3]
We demonstrated that PMC assist metastasis formation in the peritoneal cavity by forming a tumor permissive microenvironment [3,12]
We asked whether PMC can enhance the in vitro growth of MKN45, and found that the presence of PMC significantly increased the proliferation and reduced apoptosis by PMC only when MKN45 were cultured at low density
Summary
The peritoneal cavity is a common target of metastatic gastrointestinal and ovarian cancer cells [1,2,3]. Peritoneal metastasis is likely to develop from intraperitoneal free tumor cells exfoliated from the serosal surface of primary tumors [4,5], the mechanisms leading to peritoneal metastasis have not been fully elucidated. The peritoneal cavity is the largest free space in the human body. It contains a large amount of adipose tissue and is covered by mesothelium, which has a smooth and nonadhesive surface that facilitates intracoelomic movement. The peritoneal cavity physiologically contains various free cells which may have positive.
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