Specific Features of Ovarian Cancer Metastasis

Abstract

This review presents data on the predominant mechanisms of metastatic progression of ovarian cancer. The morphological and functional features of the greater omentum are shown, both promoting the spread of cancer cells and having an antitumour effect. The ratio of these two mutually opposite properties depends on the cellular composition, the content of extracellular matrix molecules and the biomechanical properties of the greater omentum during carcinogenesis. Milky spots are the main site of cancer cell implantation. They differ from lymph nodes in a simpler structure and a unique cellular composition (macrophages, B cells, CD4 + and CD8 + T lymphocytes, other immune cells) changing significantly during metastasis. М2­macrophages, adipocytes, CD33 + and CD4 + CD25 high CD127 low Т­suppressors promote migration, invasion, growth and colonization of cancer cells. The majority of the molecules synthesized in the greater omentum during metastasis also stimulate this process. The exceptions are E­cadherin, CXCL10, CXCL11, CXCR3, which inhibit the growth of tumour foci. In addition, CD8 + T lymphocytes and M1 macrophages also have antitumor effects. Since ovarian cancer is characterized by high mortality, mainly due to metastases, the issue of optimizing methods for predicting the treatment effectiveness depending on the cellular composition and expression of specific molecules in the milky spots of the greater omentum is urgent. These indicators can be applied in clinical practice using molecular genetic and immunohistochemical methods. In order to determine the need for omenectomy in the surgical treatment of ovarian cancer and to predict the outcome, it is advisable to study the morphological and functional properties of the greater omentum and to determine the number of immunocompetent cells and the nature of the expression of genes associated with the worst prognosis, those encoding activin­A, N­cadherin, CCL23, CD36, CD44, CF­1/M­CSF, FABP4, GRO­α, GRO­β, IL­8, ITGA2, MMP9, TP53, VEGF, VEGFR. These molecules are associated with adhesion and angiogenesis systems that play a key role in metastasis. Promising directions in the therapy of metastatic ovarian cancer can be stimulation of the transition of M2­ to M1­macrophages, activation of the anti­tumour antigen­specific response of CD8 + T cells using phagocytes, adaptive transfer of natural killer cells, the use of inhibitors of Wnt pathways, CCR1, CD36, FABP4, PAD4, ITGA2.