Abstract
Epithelial ovarian cancer (EOC) is a significant cause of cancer related morbidity and mortality in women. Preferential involvement of peritoneal structures contributes to the overall poor outcome in EOC patients. Advances in biotechnology, such as cDNA microarray, are a product of the Human Genome Project and are beginning to provide fresh opportunities to understand the biology of EOC. In particular, it is now possible to examine in depth, at the molecular level, the complex relationship between the tumor itself and its surrounding microenvironment.This review focuses on the anatomy, physiology, and current immunobiologic research of peritoneal structures, and addresses certain potentially useful animal models. Changes in both the inflammatory and non-inflammatory cell compartments, as well as alterations to the extracellular matrix, appear to be signal events that contribute to the remodeling effects of the peritoneal stroma and surface epithelial cells on tumor growth and spread. These alterations may involve a number of proteins, including cytokines, chemokines, growth factors, either membrane or non-membrane bound, and integrins. Interactions between these molecules and molecular structures within the extracellular matrix, such as collagens and the proteoglycans, may contribute to a peritoneal mesothelial surface and stromal environment that is conducive to tumor cell proliferation and invasion. These alterations need to be examined and defined as possible prosnosticators and as therapeutic or diagnostic targets.
Highlights
The peritoneum and its structures are integral to the microenvironment of epithelial ovarian cancer (EOC)
The metastases may be exophytic with direct exposure to the peritoneal cavity and its contents or subperitoneal foci coalescing over time to form variably sized plaque-like deposits (Figure 1)
SmFuiegrnguticrfaeoll1rloewstiangginpgriboyrlsaypsatreomscicopchye(mpeortihtoenraopsycopy) and histopathologic findings showing different patterns of peritoneal involveSurgical restaging by laparoscopy and histopathologic findings showing different patterns of peritoneal involvement following prior systemic chemotherapy. (A,B) Exophytic peritoneal metastases approximately 1 cm in diameter showing multiple capillary loops
Summary
FHiigstuorcehe2mical staining of human ovarian tissue with anti-6-sulfate chondroitin or anti-smooth muscle α-actin antibody Histochemical staining of human ovarian tissue with anti-6-sulfate chondroitin or anti-smooth muscle α-actin antibody. The transformed human ovarian surface epithelial cells recapitulated many features of natural ovarian cancer including a subtype of ovarian cancer histology, formation of ascites, CA125 expression, and NF-κB-mediated cytokine activation These cells provide a novel model system to study human ovarian cancer. Susceptibility of the stromal compartment of the peritoneum to proliferative signals has been well documented in animal models of the peritoneal fibrosing syndrome following exposure to chemical peritoneal dialysates [9,56] In these models, alterations to the stromal environment occur in response to the dialysate resulting in infiltration of two main cell populations, fibroblasts secreting MCP-1, VEGF, and HSP47 and macrophages which can express TGFβ, TNFα, IL1 and fibronectin. Future strategies should attempt to identify those pathways and networks in the microenvironment that are critical to tumor cell survival
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