Figure 1.

The ECM becomes dysregulated during ovarian tumorigenesis and contributes to tumor progression. The normal ovarian ECM consists of a highly ordered arrangement of collagen fibers, with hyaluronan interspersed throughout, regulating the distribution of the collagen in the ECM. Several proteoglycans, such as decorin and versican, are present to provide pressure and hydration to the tissue. In EOC, stromal fibroblasts are activated; collagen becomes progressively remodeled into short thick fibrils, randomly orientated into tracks at angles tending toward perpendicular rather than parallel to the epithelial boundary. In addition, versican, fibronectin, tenascin-C, and tenascin-X are upregulated with the loss of decorin. Reduced levels of HYALs lead to accumulation of hyaluronan; upregulation of LOXs leads to increased crosslinking of the ECM proteins resulting in increased stiffness of the ECM. MMPs are overexpressed in the EOC ECM, actively remodeling the ECM to promote tumor progression while TIMPs are unable to restrain these enzymes from dysregulating the ECM.