Adhesion molecules.
The exact mechanisms by which serous ovarian cancer cells invade through their underlying basement membrane or are released from the surface of the ovary have yet to be elucidated. This process undoubtedly has a complex molecular basis that most likely involves multiple cell surface receptors, basement membrane components, intercellular adhesion molecules, and signaling from the cell [137]. One possible mechanism by which ovarian carcinoma tumor cells may alter their basement membrane is by the synthesis and secretion of proteolytic enzymes that degrade their basement membranes [88-94, 138]. Alternatively, metastatic ovarian carcinoma cells may decrease their synthesis and/or secretion of ECM molecules. Additional studies are required to determine whether the more aggressive behavior of malignant ovarian carcinoma cells, compared to normal ovarian epithelial cells, is related to an altered cellular response towards ECM molecules, perhaps due to alterations in adhesion molecules/receptors. A further elucidation of the mechanisms by which serous ovarian carcinoma cells regulate their expression of ECM molecules and adhesion molecules/receptors will help in our understanding of the invasion and metastasis of tumor cells. Members of several families of adhesion molecules have been described that seem to be important in the progression of ovarian carcinoma, including CD44, integrins, and E-cadherin. Due to the complexity of this disease, it is likely that other adhesion molecules will also be implicated in the adhesion, migration, invasion, growth, proliferation, and apoptosis of ovarian carcinoma cells. Our group and others have shown that CD44 and the beta 1 integrin subunit play fundamental roles in the adhesion and migration of ovarian carcinoma cells to mesothelial cells and their associated pericellular matrix. Subsequent to the initial adhesion, the ovarian carcinoma cells may migrate through the layer of mesothelial cells, penetrate through the underlying basement membrane, invade into the tissue, and establish a secondary site of growth. Further studies will be required in order to fully understand the relationship of each adhesion molecule and their ligand(s) in the progression of this disease. Once the adhesion molecules and their ligand(s) for each step of the progression of this disease have been identified, it should be possible to develop reagents that can inhibit these interactions. Then, when ovarian carcinoma cells can no longer interact with mesothelial cells and their associated ECM, the dissemination of ovarian carcinoma cells in vivo may be prevented.
Skubitz
Amy P N
AP
Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
D017209:Apoptosis; D015820:Cadherins / Q000096:biosynthesis / Q000494:pharmacology*; D002277:Carcinoma / Q000235:genetics / Q000503:physiopathology*; D015815:Cell Adhesion Molecules / Q000494:pharmacology*; D002450:Cell Communication; D002455:Cell Division; D004848:Epithelium / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000502:physiology; D006820:Hyaluronic Acid / Q000096:biosynthesis / Q000494:pharmacology*; D016023:Integrins / Q000502:physiology*; D008024:Ligands; D010051:Ovarian Neoplasms / Q000235:genetics / Q000503:physiopathology*; D010537:Peritoneum / Q000166:cytology
D015820:Cadherins; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D016023:Integrins; D008024:Ligands; D006820:Hyaluronic Acid