Peritoneal inflammation - A microenvironment for Epithelial Ovarian Cancer (EOC)

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.

Figure 1

Surgical restaging by laparoscopy (peritonoscopy) 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. Histologic evaluation demonstrates numerous blood vessels surrounded by tumor cells. (C,D) Small 1 mm sized peritoneal metastases that are subperitoneal on histologic evaluation. (E,F) Multiple metastases about 1 cm in diameter that are growing deep to the peritoneal surface and coalescing to form plaques. Histologic evaluation demonstrates that these lesions are relatively avascular and contain significant amounts of peritumoral fibrosis. (Reprinted with permission from Cytokine, Cellular & Molecular Therapy).

Figure 2

Histochemical staining of human ovarian tissue with anti-6-sulfate chondroitin or anti-smooth muscle α-actin antibody. Serial 5-μm sections of paraffin-embedded tumors were stainead with anti-6-sulfate chondroitin (A) or anti-smooth muscle α-actin (B). Arrows point to regions of staining overlap. (Reprinted with permission from Clinical Cancer Research).